Flow balancing devices, methods, and systems

ABSTRACT

The disclosed subject matter relates to extracorporeal blood processing or other processing of fluids. Volumetric fluid balance, a required element of many such processes, may be achieved with multiple pumps or other proportioning or balancing devices which are to some extent independent of each other. This need may arise in treatments that involve multiple fluids. Safe and secure mechanisms to ensure fluid balance in such systems are described.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.16/317,903, filed on Jan. 15, 2019, which is a U.S. national stagefiling under 35 U.S.C. § 371 of International Application No.PCT/US2017/042683, filed Jul. 18, 2017, which claims the benefit of U.S.Provisional Application Nos. 62/524,518 filed Jun. 24, 2017 and62/363,394 filed Jul. 18, 2016, all of which are hereby incorporated byreference in their entireties.

STATEMENT OF GOVERNMENT SUPPORT

This invention was made with government support under HR0011-13-C-0023awarded by Department of Defense/Defense Advanced Research ProjectsAgency (DOD/DARPA). The government has certain rights in the invention.

BACKGROUND

A basic function of many extra corporeal blood treatment systems (ECBTsystems), including hemodialysis, hemofiltration, hemodiafiltration,apheresis systems, etc., is the maintenance of the overall fluid balancebetween the fluid added to the patient and the fluid withdrawn from thepatient. Ideally, this exchange will result in a net loss or gain offluid to/from the patient that precisely matches the patient's treatmentrequirement. To achieve this, the ECBT may employ a volumetric fluidbalancing system, of which a variety of different types are known. Forexample, see U.S. Pat. Nos. 5,836,908, 4,728,433, 5,344,568, 4,894,150,and 6,284,131, each of which is hereby incorporated by reference as iffully set forth in their entireties herein.

Fluid balancing mechanisms generally attempt to ensure that the totalmass or volume of fluid pumped into, and removed from, the non-bloodside of a filter or dialysis are equal. To provide for a desireddifferential between the net quantity removed/added, the inflow andoutflow rates can be controlled to produce a net difference. This may beprovided by regulating the relative flow rates provided by ingoing andoutgoing pumps or by using a separate bypass, driven by a separate pump.In an example, such a bypass pump pumps at an ultrafiltration (“UF”)line rate which is added to the balanced withdrawal rate.

Gravimetric systems that balance flow by weighing mass from a source andcollected fluid from the treatment device and comparing the two areknown. Another approach is to measure incremental volume transfer. Hardplumbed or disposable lined balance chambers alternately fill and emptyin a manner that assures equal and opposite volume exchange. Systemsusing this approach are balancing a single inlet fluid flow with aneffluent stream. A second stream of fluid is frequently added to theextracorporeal circuit using an additional pump, or external IV pump.The volume of this second stream may be balanced by the isolatedultrafiltration (UF) pump in an attempt to maintain patient fluidbalance. This approach is limited by the calibration inaccuracies of theadditional or external pump and the isolated UF pump. These inaccuraciesare acceptable at low flow rates. However, at higher flow rates thecumulative volumetric inaccuracies may not achieve the desired patientvolumetric balance. Additionally, this approach requires an operator toindependently set the pump rates to achieve the desired balance.

SUMMARY

The disclosed subject matter described in this disclosure is analternate approach to volumetric fluid balance using multiple volumetricor fixed-displacement pumps to control inflows and outflows from anextracorporeal circuit that have corresponding pump rates synchronizedrelative to each other to assure balanced flow rates.

In certain systems, volumetric fluid balancing may be performed for asingle therapy fluid stream using a system configuration includingbalance chambers, peristaltic pumps, and mechanically controlled pinchvalves. The therapy fluid entering the blood path of the extracorporealcircuit may be balanced with effluent removed from the blood paththrough the dialyzer of the circuit so that the patient volume is notaffected by this exchange of fluids. The limitation to a single therapyfluid inlet flow is a common limitation of various dialysis machinesthat use balance chambers. Some extracorporeal therapies can use morethan one therapy fluid inlet flow that may be volumetrically controlledto achieve an overall patient fluid balance. For example, the differencebetween the total fluid that moves into the patient (for example, byflowing into the patient's blood stream) and that withdrawn from thepatient must be precisely controlled. For example, in dialysistreatment, the amount of fluid entering the patient, for example throughpredilution, post-dilution, citrate infusion, and reverseultrafiltration streams may be balanced against the net ultrafiltrationstream to achieve a target net ultrafiltration rate. The subject matterdescribed in this disclosure provides alternate machine configurationsthat support one or more therapy fluid flows synchronized with theeffluent fluid flow from the extracorporeal circuit to achieve accuratefluid balance.

The disclosed subject matter includes several different systemconfigurations that support one or more therapy fluid inlet flowsbalanced with the effluent flow by diverting each therapy flow pumpindividually using a valving/flow diversion mechanisms that flow fluids,including blood and/or treatment fluid treatment configuration into aseries configuration in which fluid is pumped from one pump to anotherand the pumping rates synchronized using an imbalance detection device.One imbalance detection is the change in weight of fluid accumulatingdue to back-up of the serial flow. Another imbalance detection is thepressure buildup due to fluid volume accumulation caused by back-up ofthe serial flow. In other embodiments, pumps are individually calibratedat relevant times (one or more times per treatment for example) againsta common or gold standard flow rate measurement device. In still otherembodiments, imbalance is detected during treatment without establishinga special configuration by directly measuring the flow rates of fluid,directly by flow measurement or indirectly by measuring pressure changesto infer balanced or imbalanced flow conditions from a temporal trendwhich can be predict the magnitude of imbalance. For example, one of thepumps can be incrementally stepped, the pressure change or fluid weighttrend sampled for a period of time for each step, to establish a trend,and perfect balance fitted to the trend in order to back out thesynchronized flow rates arithmetically. Any type of fitting function maybe used such as a straight line or polynomial. When pumps aresynchronized, the operating condition are maintained to ensure thesynchronization conditions, for example suction pressure, are comparableto those during synchronization.

In embodiments, reliable flow balance is obtained by synchronizing thepump flows and using the pressure sensor to synchronize the rates ratherthan enforcing a fixed-volume flow channel. A controller connected tothe pressure sensor and pumps adjusts the effluent flow pump to thedesired flow rate and the selected therapy fluid flow pump to achieve adesired pressure between the pumps and holds the pressure stable for aperiod of time to achieve a synchronization flow value for the therapyfluid pump. This can be repeated for one or multiple inlet pump pressurevalues and stabilization times to achieve a synchronization curve forthe therapy fluid flow pump versus pressure. Alternatively, it can bedone for a single condition that is to be maintained during treatment.If the system needs to change operation state due to an uncontrolledchange such as a change of flow resistance of a patient access or acontrolled change such as a shift to a lower or higher flow rate, newsynchronization at the new condition may be performed. Oncesynchronized, small excursions from the synchronized condition thatoccur thereafter, for example during treatment, will be adjusted—for,such as when the rates of the pumps that were synchronized duringsynchronization are varied from their absolute or relative operatingspeeds, for example to provide a selected ultrafiltration rate. Theaccommodation is provided by continuously performing pump pressurecompensation, which refers to recalculating the relationship between thecommanded flow rate (or equivalent such as shaft speed or cycle ratedepending on the type of pump) and estimated actual flow rate based onknown or measured pump curves. The pump curves may flow versus outletminus inlet pressure or flow versus inlet pressure only. Othervariations are possible depending on the type of pump. In variations,the synchronization process may be triggered by change in arterialpressure, blood treatment device blood side pressure, blood treatmentdevice treatment fluid side pressure, or after a time interval. Suchtriggered synchronizations may be done for prescribed (i.e., predefined)blood and treatment fluid flow rates only so that a synchronizationprocess over multiple conditions is not required. This “spotsynchronization” process is particularly relevant in combinationsynchronization processes where no bypass flow is established so thattreatment does not have to be significantly disrupted as described belowwith reference to FIG. 8 , for example. Synchronization may be doneduring a priming operation, during treatment, or both. Spotsynchronization may be done after a period of time over a treatment aswell. The reason for triggering a synchronization after a period of timein the absence of any other change may be, for example, changes inmaterial properties over time or due to extended use, for example aplastic pumping tube segment may exhibit changes in characteristics overcontinued use during a treatment. Thus to maintain accuracy ofbalancing, a synchronization may be performed after a time estimated toensure that the amount of change is limited.

In embodiments, rather than continuously or repeatedly readjusting theflow rates of pumps to compensate for inlet pressure variation, thecumulative error caused by variations in pumping rates over a treatmentinterval are calculated and stored over time. Then the pumping rates areadjusted at a single time (at several times) for a calculated period oftime to compensate for the impact of the error on total ultrafiltrationthat occurred over the treatment interval. The step-wise correction maybe done in a single operation at one time toward the end of a singletreatment interval or multiple times over multiple treatment intervalsinto which a single treatment session is divided. These operations maybe done automatically without operator intervention. The treatmentintervals may be defined according to events such as shutdowns due toautomatic alarms or operator commands. For example, the pumping ratesmay be adjusted according to cumulative effect of error prior to ashutdown by adjusting the pumping rates immediately after restart. Also,compensation by adjusting the pumping rates can be done multiple timesat regular intervals or at other predefined times during a treatment.

Once synchronized, the pumps rates may be changed to implement apredefined difference in commanded pump speeds according to a storedpump curve. The pump curve is not limited to a stored formula oralgorithm but may also be implemented as a look up table or equivalent.The difference in commanded pump speeds is adapted to provide for aprescribed or otherwise provided ultrafiltration rate. The differentspeeds may provide for a desired fluid balance outcome in theextracorporeal circuit (neutral, positive, or negative balance). Inembodiments, the difference in speed may be limited to a minorfractional difference (i.e., less than 50% speed difference) and may belimited to fractional differences of less than 20% or 10% to ensure andimprove accuracy during treatment. In any of the embodiments, thesynchronization may include multiple flow, for example, a predilutionflow of replacement fluid which would flow into a patient's blood duringtreatment, plus a fresh dialysate flow and synchronized with a flow ofwaste. As indicated, the pump rates may be further compensated toaccount for transient effects such as changes in inlet/outlet pressures,changes due to pump life, and other factors. A compliant accumulator oradditional tubing lengths can be used to reduce pressure spikes and aidin achieving stable pressure control during the synchronization process.

The embodiments are applicable to synchronization of series (seriallyinterconnected through a treatment device) blood pumps or seriestreatment fluid pumps. In embodiments, directly flow between the seriespumps is provided by halting flow through lines that exchange fluid withthe flow path connecting the series pumps to be synchronized. Forexample, two series blood pumps connected to a filter have a fixedvolume path between then when flow through lines connected to thenon-blood side is prevented, such as by halting one or more treatmentfluid pumps, clamping one or more treatment fluid lines, or both. Foranother example, two series treatment fluid pumps connected to a filterhave a fixed volume path between then when flow through lines connectedto the blood side is prevented, such as by halting one or more pumps,clamping one or more blood lines, or both. The fixed volume can beimplemented by any suitable means for halting flow on the other side(other side of the pumps used for balancing) of the treatment fluiddevice including halting inflow and outflow pumps on said other side orhalting a single pump such as an inflow pump and clamping the otherline, such as an outflow line. These may depend on the configuration.

All pumps may be equipped with an inlet pressure sensor and may also befitted with an outlet pressure sensor to support pressure compensationof the pump rate. In a pressure compensation method, the flow rate ofthe pump may be derived from the pump rotation or reciprocation rate andadjusted responsively to the inlet and/or outlet pressure. Thisderivation and compensation may be done using a single function of bothpressure (inlet, outlet, or pressure change) and rotation speed. Forexample, the function may be embodied in a look up table stored in adata store of a controller. Additionally, the control valves may beclosed so that pump occlusion may be confirmed by the reading of thevarious pressure sensors.

In embodiments, flow is halted in the non-blood compartment of atreatment device and an average blood compartment pressure isestablished by flowing fluid through the blood compartment of thetreatment device by pumping fluid into the blood compartment and with apredefined resistance at the outlet of the blood compartment. Thisaverage pressure is stored as a target. The dialysate compartmentpressure is affected by the oncotic pressure caused by the presence ofprotein in the blood. Fresh and waste treatment fluid pumps connected tothe non-blood compartment are then synchronized by commanding the wastetreatment fluid pump to a predefined treatment fluid flow rate andadjusting the fresh treatment fluid pump rate until the target averageblood compartment pressure is restored in the blood compartment. Inalternative embodiments, the target may be established from thetreatment fluid pressure (e.g., taking an average of the inlet andoutlet treatment fluid pressure at the inlet and outlet ports of thetreatment fluid device). By measuring the difference between treatmentfluid device treatment fluid compartment pressure and blood compartmentpressure during zero (or near-zero) transmembrane flow conditions,oncotic pressure may be directly determined. The technique may be usedto determine the oncotic pressure which may be used as well for otherpurposes, such as determining the magnitude of ultrafiltration required(i.e., how much excess fluid is in the patient's blood—hypervolemia).The synchronized fresh treatment fluid pump rate is recorded. Thisprocedure may be repeated for multiple predefined pumping rates andblood compartment pressures to record a table of blood compartmentaverage pressures and predefined treatment fluid flow rates as theindependent variables (e.g., rows and columns although any data storageelement may be used) and a corresponding synchronized fresh treatmentfluid flow rate for each combination (e.g., recorded in the cells of thetable). The data may be fitted to a function to estimate a synchronizedfresh treatment fluid pumping rate for any prescribed combination oftreatment fluid flow rate and blood flow rate through the bloodcompartment, which will correspond, during treatment, to an averagepressure of the blood compartment. When treatment is performed, theaverage blood compartment pressure is measured and applied to the fittedfunction, with a prescribed treatment fluid flow rate, to obtain anestimated fresh treatment fluid flow rate. A modified waste treatmentfluid flow rate is then calculated to provide for a prescribedultrafiltration rate. The pumping rate of the waste treatment fluid flowrate may be generated from a function of inlet pressure and target flowrate that provides a command flow rate to be applied to the pump. Suchfunctions are commonly used for controlling peristaltic pumps. The stepin commanded flow required by the waste treatment fluid pump to achievethe required ultrafiltration may be calculated from such a function andthe current waste treatment fluid inlet pressure, then the wastetreatment fluid pump commanded correspondingly. The new inlet pressuremay be fed back iteratively to obtain a refined command flow for thewaste treatment fluid pump until the inlet pressure stops changingwithin a predefined interval. Whenever, during treatment, the averageblood compartment pressure changes beyond a predefined threshold, thefresh treatment fluid pump rate may be adjusted to return the averageblood compartment pressure to the target and the waste treatment fluidpump rate reestablished iteratively as above. If the average bloodcompartment pressure changes beyond a greater threshold, the freshtreatment fluid pumping rate may be recalculated based on the prescribedtreatment fluid flow rate as above and the waste treatment fluid pumpingrate adjusted iteratively as above based upon a prescribedultrafiltration rate.

The principles of the subject matter disclosed herein are applicable toboth peristaltic pumps with disposable fluid pathways as well as hardplumbed systems and combinations of the two. In a hard plumbedconfiguration, the flow path components may require disinfection similarto standard dialysis machines and would require special techniques tomeet the requirements for direct infusion of therapy fluids.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments will hereinafter be described in detail below with referenceto the accompanying drawings, wherein like reference numerals representlike elements. The accompanying drawings have not necessarily been drawnto scale. Where applicable, some features may not be illustrated toassist in the description of underlying features.

FIG. 1A shows a blood treatment system that regulates the flow of bloodinto and out of a treatment device to generate a cumulative target ratioof fluid drawn or infused into a patient over the course of a treatmentaccording to various embodiments of the disclosed subject matter.

FIG. 1B shows the system of FIG. 1A in a configuration, implemented bythe controller, for synchronizing pumps with only one fluid sourceaccording to various embodiments of the disclosed subject matter.

FIG. 1C shows the system of FIG. 1A in a configuration, implemented bythe controller, for synchronizing pumps with more than one fluid sourceaccording to various embodiments of the disclosed subject matter.

FIG. 2A shows a flow chart of a control method for delivering atreatment while providing balanced flows of independently-controlledpumps where two pumps, an inlet and outlet, are balanced according tovarious embodiments of the disclosed subject matter.

FIG. 2B shows a flow chart of a control method for delivering atreatment while providing balanced flows of independently-controlledpumps where multiple inlet pumps are balanced against one outlet pumpaccording to various embodiments of the disclosed subject matter.

FIG. 3A shows a flow a blood treatment system that regulates the flow oftreatment fluid into and out of a treatment device to generate acumulative target ratio of fluid drawn or infused into a patient overthe course of a treatment according to various embodiments of thedisclosed subject matter.

FIGS. 3B through 3E illustrate configurations of the blood treatmentsystem of FIG. 3A at various phases of a synchronization sequenceaccording to embodiments of the disclosed subject matter.

FIGS. 4A through 4D are flow charts for discussion of synchronizationoperations discussed with reference to FIGS. 3B through 3E according tovarious embodiments of the disclosed subject matter

FIG. 5 shows a flow meter adapted for use in blood treatment systemsaccording to embodiments of the disclosed subject matter.

FIGS. 6A and 6B show a blood treatment system that regulates the flow oftreatment fluid to generate a cumulative target ratio of fluid drawn orinfused into a patient over the course of a treatment in a treatmentmode and a synchronization mode, respectively, according to furtherembodiments of the disclosed subject matter.

FIG. 7 is for describing certain principles of operation of thecontroller and blood treatment apparatus, according to embodiments ofthe disclosed subject matter.

FIG. 8 shows a method for synchronizing fresh and waste treatment fluidpumps during a treatment, according to embodiments of the disclosedsubject matter.

FIG. 9 shows a programmable control system with details that may beinherent in any of the controller embodiments disclosed herein andaccording to various embodiments of the disclosed subject matter.

FIGS. 10A and 10B illustrate the generalization of the flow balancingscheme in which blood side or non-blood side inflow and outflow pumpsmay be used to regulate the fluid balance according to embodiments ofthe disclosed subject matter.

FIG. 11 shows a blood treatment machine figuratively with variousactuators and sensors and an attached fluid circuit according toembodiments of the disclosed subject matter.

FIG. 12A-12C show elements of a hemofiltration system or ahemodiafiltration system, the elements being common to, but not limitedto, the multiple stream system of FIG. 11, for purposes of describing asynchronization procedure for balancing flow for a hemofiltrationtreatment according to various embodiments of the disclosed subjectmatter.

FIG. 12D-12G show elements of a hemodiafiltration system, the elementsbeing common to, but not limited to, the multiple stream system of FIG.11 , for purposes of describing a synchronization procedure forbalancing flow for a hemodiafiltration treatment according to variousembodiments of the disclosed subject matter.

FIGS. 13A-13C show the abstract elements and processes for pumpbalancing according to various embodiments of the disclosed subjectmatter.

FIGS. 14A-14B illustrate synchronization dynamically by sampling andextrapolating from a synchronization signal in order to reduce the timeof pump synchronization, according to various embodiments of thedisclosed subject matter.

FIGS. 15A-15C show a system and method in which a zero transmembraneflow is established without halting the flow of treatment fluidaccording to various embodiments of the disclosed subject matter.

FIG. 16 shows a method of calculating to maintain an ultrafiltrationbudget over the course of multiple pump synchronization, according tovarious embodiments of the disclosed subject matter.

FIGS. 17A-17B illustrate command rate vs. time graphs for purposes ofdiscussing a method of calculating to maintain an ultrafiltration budgetover the course of multiple pump synchronization, according to variousembodiments of the disclosed subject matter including the embodiments ofFIG. 16 .

FIGS. 18A-18B illustrate the generation and use of a map of commandedflow and pressure conditions for determining the synchronized commandspeed of a slave pump according to various embodiments of the disclosedsubject matter.

DETAILED DESCRIPTION

FIG. 1A shows a blood treatment system 100 that regulates the flow offluid in a fluid circuit 121 that includes an arterial blood line 139, avenous blood line 137, a fresh treatment fluid line 127 and a wastetreatment fluid line 125. In particular, the blood treatment system 100regulates the flow of fluid across a membrane of a treatment device 114to generate a cumulative target ratio of fluid drawn from, or infusedinto, a patient over the course of a treatment. During set-upprocedures, instead of a patient being hooked up to the connections 122and at those times, or in that case, 122 identifies sources and sinks(or a recirculating container) of priming fluid. The control of thepumps provides a net flow of fluid across a membrane (and concomitantlyto/from a patient or priming fluid source/sink). Hereafter it should beunderstood that in any of the embodiments, any reference to “patient”and/or “blood” with reference to a fluid balancing or pumpsynchronization may be replaced by priming fluid and/or a combinationsource and sink thereof, because the fluid balancing and synchronizationmode/operation modes discussed herein can be done during priming as wellas using blood during a treatment. It should also be understood that thepriming fluid source/sink may be a single recirculating channel orchamber as well as a single-pass arrangement with a separate source andsink. At any given time, the net rate of flow across the membrane(identified in renal treatment as the ultrafiltration rate) isdetermined by a then-instant difference between the volume of bloodpumped out of a treatment device 114 (for example a dialyzer) to thevolume of blood pumped into the treatment device 114 plus the fluidpumped into the blood lines. The ultrafiltration rate may also beunderstood as the total amount of fluid transferred from the patienttaking into account any replacement fluid 120 and/or other fluid(supplemental fluids SF1 and SF2 such as anticoagulant or drug) that isconveyed directly to the patient's blood.

Returning to FIG. 1A, blood is pumped into the treatment device 114 byan arterial blood pump 110 and pumped from the treatment device 114 by avenous blood pump 104. The illustrated configuration is common fordialysis systems, and may include all the typical incidents thereof, butdiffers specifically in that there are two blood pumps: the arterialblood pump 110 and the venous blood pump 104.

During a treatment mode and also in embodiments of a synchronizationmode, blood is pumped to and from a patient access 122. In otherembodiments synchronization may be performed, instead, with a primingfluid. During priming operations, the patient access or primingconnector(s) may be connected to priming fluid source, sink, orrecirculating container instead. Thus, 122 may be considered generallyto represent a patient access connected to a patient, in which case thecirculating fluid is blood, or 122 may be at other times a priming fluidsource, sink, or recirculating container, in which case, the circulatingfluid would be priming fluid.

Control and sensing are provided by a controller 140 which may be of anyform but typically some type of programmable digital controller, forexample, an embedded computer. A treatment fluid is pumped from atreatment fluid source 124 through an air detector 118 (also referred toas an air sensor) through the treatment device 114, past a waste lineclamp 130, to the drain 126 (indicated by W for waste). The pumps,clamp, and all sensors may be connected for control and input by thecontroller 140. Drain 126 may be a drain of a plumbing system or acollection container or any other device for disposal of waste treatmentfluid. Treatment fluid 124 may be dialysate, replacement fluid, or anyother medicament.

A replacement fluid 120 may be pumped into the arterial blood line 139or the venous blood line 137 through a replacement fluid line 135 or138, respectively (or both) for predilution, post-dilution or acombination of both. In alternative embodiments, the dilution may occurat a midpoint of the treatment device 114, for example in a case wherethe treatment device 114 were composed of two smaller units thatprovided a fluid connection junction between them to admit fluid at thatpoint to the blood compartment. A mid-dilution treatment device may havea special construction to provide for mid-dilution. The treatment device114 may be adapted for a variety of types of blood treatment thatrequire balancing flows into and out of a patient blood compartment,including, but not limited to, dialysis, hemofiltration,hemodiafiltration, apheresis, adsorption, or hemoperfusion. Thesetreatment modalities may apply as alternatives to any of the disclosedembodiments including those originally disclosed in the claims. Furthersupplemental fluids indicated by supplemental fluid 134 and supplementalfluid 132 may be pumped into the arterial blood line 139 by respectivepumps, namely, a supplemental fluid pump 142 and a supplemental fluidpump 144, either or both of which may be present. Examples ofsupplemental fluids are drugs and anticoagulant (e.g., citrate,heparin).

Pressure sensors may be provided at various points throughout the fluidcircuit 121. In particular, an arterial pressure sensor 112 may detectpressure of the blood in the arterial blood line 139 upstream of thearterial blood pump 110. In embodiments, each pump contributing to flowbalance may have a pressure sensor up stream of it to ensure thatpressure compensated control of its speed can be provided. For example,an additional treatment fluid pump pressure sensor 119 may be provided.In embodiments, pressure sensors used for pressure compensated speedcontrol are positioned such that they provide a reliable and consistentindication of pressure upstream of the respective pump or pumps. Thus,they may be positioned close or at least such that there are nointervening possible interferences such as tube lengths that couldbecome kinked. A blood inlet pressure sensor 108 may detect pressure ofthe blood in the arterial blood line 139 downstream of the arterialblood pump 110 and upstream of the treatment device 114. A blood outletpressure sensor 106 may detect pressure of the blood in the venous bloodline 137 upstream of the venous blood pump 104 and downstream of thetreatment device 114. A venous blood pressure sensor 102 may detectpressure in the venous blood line 137 downstream of the venous bloodpump 104 and upstream of the patient access 122. The controller 140receives signals from each of the arterial pressure sensor 112, bloodinlet pressure sensor 108, blood outlet pressure sensor 106, and venousblood pressure sensor 102 as well as an air detector 118 that ispositioned to detect air in the fresh treatment fluid line 127. Thecontroller 140 is also connected to control each of the arterial bloodpump 110, venous blood pump 104, replacement fluid pump 116,supplemental fluid pump 142, and supplemental fluid pump 144, as wellthe waste line clamp 130.

Note that the waste line clamp 130 could be replaced by any type ofvalve that selectively halts or permits flow or another pump. Note thatthe pressure sensors may be of any of a variety of types of pressuresensors used for indicating pressure in a fluid circuit, for examplebubble chambers, pressure pods (e.g. U.S. Pat. No. 8,092,414), and thelike.

In alternative configurations, instead of treatment fluid pump 128 andwaste line clamp 130 being used to halt flow as described below, a wastefluid pump may be provided in the position of waste line clamp 130,which can halt flow by halting rotation. In any of the embodiments,including the present and further embodiments to be described below ordescribed above, any element identified as a line or fluid line (orfluid circuit) could be any type of flow channel includinginterconnected tubes including pumping tube segments, channels formed ina cartridge (as a pattern of troughs sealed by an overlying weldedfilm), a pattern-welded pair of weldable sheets, a laminated stack ofelements that defines flow channels, or any other device that guides theflow of fluid. Any element identified as a pump may be any type of pumpor actuator that is volumetric aka, positive displacement type. Suchembodiments of lines and fluid lines or fluid circuits may be disposableor otherwise replaceable components that engage pumps, sensors, andactuators of a treatment machine that includes such pumps, sensors, andactuators as identified in the embodiments. Such a machine may beillustrated schematically in the drawings, but not necessarily as aseparate component, for example a pump indicated by a single element mayinclude a pump actuator, e.g., a rotor, that works together with a pumptubing segment of a fluid circuit, while both are indicated by a pumpsymbol schematically in the drawing. Similarly, sensors and clamps arenot illustrated separately in all the drawings. Such a machine may beembodied in multiple separate components and may be generally describedas having a receiving adapter to allow the connection of a disposablefluid circuit.

The term, receiving adapter, or similar term is an abstraction that maycover all the various mechanisms that permit the operative associationbetween a permanent device and a disposable or replaceable componentwhich together form one of the apparatuses disclosed or claimed. Thisapplies to all the disclosed and claimed embodiments. For example, thedrawings described above and below illustrate a system which, whenconsidering that portions are replaceable, indicate the presence of ablood circuit receiving adapter and a medicament (treatment fluid,dialysate, or similar fluid) receiving adapter. The fluid circuits(including blood circuits) may include treatment components as well asportions that engage with sensors and actuators. Again, these commentsapply to all embodiments.

Any element identified as a pressure sensor may be a combination of afluid circuit portion such as a pressure pod or drip chamber and anelectronic transducer such as a strain gauge or displacement encoderconnected to an element such as a diaphragm that registers pressure. Theforegoing elements are well known classes of devices and furtherelaboration is not needed to permit the skilled reader to develop thedetails of working embodiments of the described subject matter. Fluidsmay be supplied from containers such as bags or inline fluid generatorssuch as used in dialysis clinics.

In a treatment operation of blood treatment system 100, arterial bloodpump 110 and venous blood pump 104 pump blood or priming fluid in thedirections indicated by the respective arrowhead of each pump symbol.They pump at rates controlled by the controller 140 to approximatelybalance (equivalently, “equalize”) the flow of blood in the arterialblood line 139 against the flow of blood in the venous blood line 137such that a net take-off of fluid (ultrafiltrate) or a net infusion offluid takes place (which may be called negative ultrafiltrate). Theinstantaneous rate of ultrafiltrate referring to net loss of fluid bythe patient and negative referring to net gain of fluid by the patient)is achieved through control of the total displaced volume by thearterial blood pump 110 relative to the venous blood pump 104. Theultrafiltrate may be established by a predetermined ratio of the flowrates of the arterial 110 and venous 104 blood pumps if the transfer isspread uniformly over the treatment interval or the net ultrafiltratemay be established in a discontinuous manner by varying the ratio of theflow rates of the arterial 110 and venous 104 blood pumps to achieve acumulative ultrafiltrate. Thus, ultrafiltrate volume is established bythe total volume transported by the venous blood pump 104 minus thetotal volume transported by the arterial blood pump 110 over the courseof a treatment. Ultrafiltrate rate may identify the instantaneousdifference between the rates of the venous 104 and arterial 110 bloodpumps.

The controller 140 may be programmed to ensure that the net volume ofultrafiltrate or infused fluid meets a prescribed target which may bestored by the controller 140. The pumping speeds required to achievecommanded flow rates may be determined by the controller 140 using datastored by the controller such as look up tables or formulas. A commandedflow rate refers to the operational property (e.g., shaft speed of aperistaltic pump) that is under directly control of the controller whichcorresponds more or less accurately to a flow rate, conditions that mayvary from those used to establish a transfer function defining therelationship between the operational property and an actual flow rateproduced by it. The conditions may include manufacturing variabilitysuch as pumping tube segment and fluid line diameter, materialproperties of the pumping tube segment, pump lubrication, as well asfactors that change due to operation history and storage such asdistortions, material creep, etc. The ratio of flow rate to pump speedmay be presented by stored look-up table data to indicate target pumpspeeds by a relationship between pressure difference and flow rate.

Treatment fluid 124 is pumped by fresh treatment fluid pump 128 at apredefined rate stored in the controller 140, which rate may be selectedto correspond to the blood flow rate. The replacement fluid 120 may bepumped at a rate controlled by the controller 140 by controlling thecommanded rate of replacement fluid pump 116. The supplemental fluid 134may be pumped at a rate controlled by the controller 140 by controllingthe commanded rate of supplemental fluid pump 142. The supplementalfluid 132 may be pumped at a rate controlled by the controller 140 bycontrolling the commanded rate of supplemental fluid pump 144. Any ofthe replacement fluid 120, supplemental fluid 134, or supplemental fluid132 are optional and may or may not be included, along with therespective lines and pumps, in alternative embodiments.

Valves or pinch clamps identified anywhere in the current patentapplication may be of any type. For example, flexible membranes closedover cartridge-embedded ports, electrically actuated pinch clampsemploying linear actuators such as solenoid plungers or stepper motoractuators may be used. The particular type of valve mechanism does notlimit the disclosed subject matter. Line 136 is present to indicate thatin alternative embodiments, the supplemental fluids may enter thearterial blood line 139 upstream or downstream of the arterial bloodpump 110.

As indicated above, in any of the embodiments, the fluid balance (netultrafiltrate volume) resulting from the flows to and from a patient isunderstood to accrue over a period of time. Thus, although in theembodiments, the controller is described as controlling pumping rates toachieve a fluid balance, optionally offset by a net transfer of fluid toor from the patient (net ultrafiltrate volume), it is understood thatthe pumping rates need not be constant, define a constant ratio overtime, or even define a smoothly varying ratio over time. Since theultimate goal is to control the total loss or gain of fluid from apatient (net ultrafiltrate volume), pumping rates can establish avariety of rates over time such that the cumulative effect is the targetultrafiltrate volume at the end of the treatment. Rates may be constantor vary step-wise, smoothly, and may result in a temporary gain of fluidby the patient during a portion of a treatment interval and net lossduring another portion to achieve a total gain or loss for the entiretreatment. For another example, the entire fluid gain or loss can beconfined to a single part of the treatment interval. The controller mayalso limit estimated ultrafiltrate so that overall balance does notexceed a certain volume at a given time. A rate of ultrafiltration mayalso, or alternatively, be limited by the controller.

FIG. 1B shows the system of FIG. 1A in a configuration implemented bythe controller 140 to synchronize the pumps for equal flow while pumpinga single fluid, blood or priming fluid 123. At the beginning of atreatment or at times during a treatment (as further discussed laterwith reference to FIGS. 2A and 2B), a synchronization procedure isperformed. The treatment fluid pump 128, the replacement fluid pump 116,supplemental fluid pump 142, and supplemental fluid pump 144 are allheld in a halted configuration to block flow (i.e., prevent flow)through a respective line into or out of the treatment device 114. Wherenon-positive displacement pumps are used, an auxiliary valve, such as apinch clamp, may be included to prevent flow and in such cases, thecombination of the non-positive displacement pump and valve may byidentified compactly in the current specification and claims as a pump.The halted flow configuration is indicated by the universal prohibitionsafety sign (/) overlying the pump symbols. The waste line clamp 130 isshown closed (again the waste line clamp 130 may be any type of valve).In this configuration, the arterial blood pump 110 and the venous bloodpump 104 are directly connected in series such that there exists a fixedvolume between the arterial blood pump 110 and the venous blood pump104.

To perform a synchronization, during a synchronization mode, thearterial and venous blood pumps 110, 104 may be initially commanded toflow at a predefined pump speed corresponding to a commanded flow rateof the blood stored by the controller 140. During preparation for atreatment, this may be done, as indicated elsewhere, using priming fluidrather than blood. It may be done during treatment using blood. Thecommanded flow rate may be one indicated for a prescription fortreatment. The latter may also be directly entered through a userinterface 141 of the controller 140. Any differences in the volume flowrates pumped by the arterial blood pump 110 and venous blood pump 104may be detected from the blood outlet pressure sensor 106, the bloodinlet pressure sensor 108, or an average of the two. That is, a risingpressure trend indicates the arterial blood pump 110 is pumping at ahigher flow rate than the venous blood pump 104 providing a feedback.Using the pressure signal, the controller may compensate by slaving oneof the venous blood pump 104 and arterial blood pump 110 to the other ofthe venous blood pump 104 and arterial blood pump 110 until the volumerates of the two pumps are equal, i.e., the pumps are synchronized. By“slaving” it is meant that one pump is PID or PD feedback-controlleduntil the flow is synchronized with that of the other pump. Thesynchronization may be performed for one, or more than one flow rate.This may be done in this embodiment and others during an initial primingstage. For each flow rate, the relative speeds of the arterial bloodpump 110 and venous blood pump 104 that correspond to identical flowrates may be recorded by the controller, for example as a ratio. Theratio corresponding to equal flows may then be compared to a predictedratio stored by the controller and a control parameter used for futurepredicted ratios of commanded flow to actual flow may be derived andstored by the controller 140 for using during treatment. Other datastructures to allow the controller 140 to determine and command one ofthe arterial blood pump 110 and venous blood pump 104 speed to beselected for a speed of the other calculated to provide a commanded flowrate of blood.

Note that in the foregoing embodiment, instead of blocking flow in thetreatment fluid lines and synchronizing blood pumps, a system maybalance flow using the treatment fluid pumps. In such a system, the flowof blood may be blocked forming a fixed volume channel between thetreatment fluid pumps for synchronization. The procedure for thisembodiments would be analogous.

Note that in all embodiments, a synchronization operation performedduring a synchronization mode as described according to one embodimentabove may provide a control parameter for treatment without fullysynchronizing the pumps. That is, the controller 140 can determine fromthe dynamic response of the pressure and commanded flow rates,sufficient information to extrapolate the control parameter. This maysave considerable time during a synchronization mode that is implementedduring treatment. Thus, a dynamic hydraulic model of the flow system mayprovide a number of equations whose unknown parameters can be fittedusing the pressure and flow rate signals over a period of time which isinsufficient to establish equal flows of the pump but sufficient toestimate the control parameter for improving the equal flow estimateduring a treatment. There are many choices for a dynamic model dependingon the conditions and level of accuracy required. An unsteadyhydrostatic model may be sufficient if pumping rates are so low as toproduce low flow resistance. Factors such as flow resistance can beincorporated using steady state equations and time-varying flow forrheological fluid and non-rheological fluids may be used)

The synchronization mode operation of FIG. 1B may be triggered byvarious indications that may be automatically detected by the controller140. For example, one trigger may be a command received from the userinterface 141 to provide an ultrafiltrate volume that corresponds to anaverage or instantaneous ultrafiltration rate that exceeds a predefinedmagnitude. For example, the ultrafiltration rate may be recalculated toachieve an ultrafiltrate volume based on a remaining treatment time. Therate may correspond to rates of pumping of the arterial blood pump 110and the venous blood pump 104 of a certain magnitude. The trigger pointfor implementing the synchronization mode may be stored as a predefineddifference between the commanded pumping rates or a ratio thereof.Alternatively, numerical bounds on absolute or relative ultrafiltration(infusion) rate may be stored and applied by the controller 140. Whenthe blood treatment system 100 is commanded to operate beyond thosebounds, the synchronization mode may be implemented. The synchronizationmode may be implemented with the additional flows of replacement fluid120, supplemental fluid 134, and/or supplemental fluid 132 as discussedbelow.

In a preferred embodiment, the synchronization process covers multipleoperating conditions and is done during priming. In this embodiment, thecontrol parameters for multiple operating conditions are used to controlthe system during treatment. The need to perform a synchronizationduring a treatment can be avoided. However, various trigger conditionsmay cause the system to perform a synchronization during a treatment.

FIG. 1C shows the system of FIG. 1A in a configuration, implemented bythe controller, for synchronizing pumps with more than one fluid source.At the beginning of a treatment or at times (determined by triggerevents) during a treatment, a further synchronization procedure isperformed. The treatment fluid pump 128, supplemental fluid pump 142,and supplemental fluid pump 144 are all held in a halted configurationto prevent flow through a respective line into or out of the treatmentdevice 114. The controller 140 calculates a speed for the venous bloodpump 104 and then the controller 140 calculates a flow rate and a pumpspeed for the operation of each of the replacement fluid pump 116 andthe arterial blood pump 110 based on a commanded ultrafiltration rate orinfusion rate. The waste line clamp 130 is shown closed (again the wasteline clamp 130 may be any type of valve). In this configuration, thearterial blood pump 110 and the replacement fluid pump 116 are connectedin series with the venous blood pump 104 such that there exists a fixedvolume between the parallel-arranged arterial blood pump 110 andreplacement fluid pump 116 and the venous blood pump 104. Thus, the flowthrough the venous blood pump 104 must match the sum of the flowsthrough the arterial blood pump 110 and replacement fluid pump 116 inorder for the pumps to be synchronized.

To perform a synchronization, the pumps may be initially commanded toflow at a predefined pump speed corresponding to a commanded flow rateof the blood stored by the controller 140 and representing aprescription for treatment. The latter may also be directly enteredthrough a user interface 141 of the controller 140. Any differences inthe volume flow rates pumped by the arterial blood pump 110 and venousblood pump 104 may be detected from the blood outlet pressure sensor106, the blood inlet pressure sensor 108, or an average of the two.Using the pressure signal, the controller may compensate by slaving oneof the venous blood pump 104 and arterial blood pump 110 toward amatched flow with the other of the venous blood pump 104 and arterialblood pump 110 until the two pump flow rates equalized as indicated bythe pressure of the fixed-volume channel. During a synchronizationcycle, the replacement fluid pump 116 may be kept at a fixed ratio or afixed rate of pumping and a slaved one of the arterial blood pump 110and venous blood pump 104 may be varied until synchronization isachieved or (equivalently) sufficient information is obtained to fit ahydraulic model that can provide the required control parameter.Alternatively, other combinations of the pumps may be halted and/oroperated to achieve a relevant target. A PID or PD algorithm, with thepressure signal as a feedback control variable, may be applied by thecontroller to achieve synchronized pumps. The synchronization may beperformed for one, or more than one flow rate. For each, the relativespeeds of the replacement fluid pump 116, arterial blood pump 110 andvenous blood pump 104 that correspond to identical flow rates may berecorded by the controller, for example as a ratio. Various datastructures may be used to store the relevant one or more controlparameters to ensure the ratio of speeds of the pumps provides a balanceor ultrafiltration rate that is required.

During any synchronization procedures, a target range for venouspressure, as indicated by venous blood pressure sensor 102, may beestablished. This pressure may be stored by the controller 140 and havea predefined magnitude that is selected based on safety or otheroperational requirements. Pumping rates may be commanded and regulatedto achieve the target venous pressure. During any of thesynchronizations and/or during treatment, a predefined flow rate of thesupplemental fluid pump 142 and supplemental fluid pump 144 may beestablished according to prescription. The rates of the supplementalfluid pump 142 and supplemental fluid pump 144 may be imposed bycontrolling the corresponding pump speeds based on a predefinedcommanded rate. Generally, the supplemental fluid pump 142 andsupplemental fluid pump 144 will not contribute sufficient volume to berelevant to include in fluid balance and thus synchronization may nottake their contributions into account. However, this may or may not bethe case.

Synchronization may be performed to provide accurate reproduction ofbalanced flow any time the operational configuration changes or willchange, including when new fluid circuits are installed, a new treatmentis begun, the flow rates are changed, a flow characteristic of a fluidcircuit component (such as flow restriction of a flow element, thepatient access, or treatment device) changes, or the commandedcharacteristics of a treatment are changed. In particular, thesynchronization of pumps that contribute significantly to the balance offluid of the patient is performed under conditions that are as close aspossible to those that exist during treatment so that thesynchronization data are valid during treatment. In embodiments, a newsynchronization may be indicated by the controller based on variablesthat are estimated or predicted rather than directly measured. Forexample, the compliance of materials may change with time and/ortemperature, for example pumping tube segments of peristaltic pumps. Sothe lapse of time may be used as a proxy for an indication of materialchanges. A pause in the operation of a machine, for example an alarmstoppage, may be a trigger for a synchronization mode immediately afterrestart.

FIG. 2A illustrates an operating scenario. A command is received by thecontroller 140 at S4 to begin a treatment. The command may be enteredthrough a user interface operated by the patient, caregiver, orclinician, or it may be received from a remote or local operatordirectly or indirectly through the user interface 141. At S6, thecontroller 140 reads prescription data from a data store, which mayinclude user profile information, data about prior treatments and otherinformation. At S16, the pumping speeds required to achieve thecommanded flow rate are calculated for each pump based on stored data.Then at S18, the pumps are run and synchronized as described. When thesynchronization is achieved, the data that permits the calculation ofpump speeds from commanded flow rates are stored and then used at S20 tocalculate the pump speeds for the treatment which is performed at S10.

Referring now to FIG. 2B, at S10 (continued from FIG. 2A), beforetreatment or at any time during a treatment if conditions change such asa commanded change in flow rate as indicated at S12, the controller 140may determine if a threshold of the flow change exceeds a predefinedrange at S14. If such an event is determined by the controller and thecontroller may perform a new synchronization procedure to generateupdated control parameter for calculating pump speeds from commandedflow rates as described above. At S16, the pumping speeds required toachieve the commanded flow rate are calculated for each pump based onstored data. Then at S18, the pumps are run and synchronized asdescribed. When the synchronization is achieved, the data that permitsthe calculation of pump speeds from commanded flow rates are stored andthen used at S20 to calculate the pump speeds for the treatment which isperformed at S10.

As indicated above, any change in conditions or a programmed lapse oftime or other condition at S12 may indicate a candidate forresynchronization. For example, at S12, venous pressure rise to apredefined level may cause the controller to self-command a flow ratereduction. An operator command may indicate a change in flow rate or achange in hemofiltration rate. An operator command to reduce treatmenttime may require the controller to calculate new flow rates andattending new synchronization. The controller may store product-specificparameters such as the fluid circuit materials or product identifierwhich may in turn indicate schedule of resynchronization. This may allowthe system to compensate for materials with known material propertydrift which can cause inaccuracy in net fluid balance over the course ofa treatment. Such compensation may take the form of more frequentpre-schedule resynchronizations of the flow rate-to-pump speed datausing pump synchronization as described.

Note that the system of FIGS. 1A-1C can be modified to place a lineclamp like waste line clamp 130 in place of the venous blood pump 104and using a pump on the waste treatment fluid line 125. In that case,fluid balancing can be done on the medicament side rather that the bloodside. The fixed volume channel can be implemented for synchronization byclamping the blood line and stopping the blood pump. In other respects,the system may operate as described above.

FIG. 3A shows a flow a blood treatment system 200 that regulates theflow of treatment fluid relative to generate a cumulative target ratioof fluid drawn or infused into a patient 122 over the course of atreatment. The blood treatment system 200 regulates the flow of fluid ina fluid circuit 221 that includes an arterial blood line 139, a venousblood line 137, a fresh treatment fluid line 127 and a waste treatmentfluid line 125. The net flow of fluid into or out of a patient orpriming source/sink, at any given time, is determined by a currentdifference between the volume of treatment fluid pumped from a treatmentdevice 114 (labeled F for filter) to the volume pumped into thetreatment device 114 plus the volume pumped into the blood lines. Fluid(blood or priming fluid) is pumped from a source (e.g., patient 122 orpriming fluid source—see later embodiments 3B et seq) into the treatmentdevice 114 by an arterial blood pump 110 and flows from the treatmentdevice 114 back to the patient 122 or priming fluid sink, drain,collection container, or recirculating container. As discussedelsewhere, for synchronization, the patient may be a priming fluidsource/sink. For example, it may be a container of priming fluid towhich priming fluid is returned thereby allowing endless recirculationand functioning as both source and sink of fluid. The illustratedconfiguration is common for dialysis systems, and may include all thetypical incidents thereof, but differs specifically in that there aretwo treatment fluid pumps: a fresh treatment fluid pump 153, which pumpsfresh treatment fluid 124 into the treatment device 114, and a wastetreatment fluid pump 154, which pumps waste (spent) treatment fluid fromthe treatment device 114 to a drain 126. As above, control and sensingare provided by a controller 240 which may be of any form and again,typically, a programmable digital controller; an embedded computer.Treatment fluid 124 is pumped from a source through an air detector 118through the treatment device 114, to the drain 126 (indicated by W forwaste).

A replacement fluid 120 may be pumped into the arterial blood line 139or the venous blood line 137 through a replacement fluid line 135 or138, respectively (or both) for predilution, post-dilution. Inalternative embodiments, the dilution may occur at a midpoint of thetreatment device 114 as discussed above. The treatment device 114 may beadapted for any type of blood treatment including, but not limited to,dialysis, hemofiltration, hemodiafiltration, apheresis, adsorption, andhemoperfusion. Further supplemental fluids indicated by supplementalfluid 134 and supplemental fluid 132 may be pumped into the arterialblood line 139 by respective pumps, namely, supplemental fluid pump 142and supplemental fluid pump 144, either or both of which may be present.Examples of supplemental fluids are drugs and anticoagulant (e.g.,citrate, heparin).

Pressure sensors may be provided at various points throughout the fluidcircuit 121. In particular, an arterial pressure sensor 112 may detectpressure of the blood in the arterial blood line 139 upstream of thearterial blood pump 110. A blood inlet pressure sensor 108 may detectpressure of the blood in the arterial blood line 139 downstream of thearterial blood pump 110 and upstream of the treatment device 114. Ablood outlet pressure sensor 106 may detect pressure of the blood in thevenous blood line 137 upstream of the venous blood pump 110 anddownstream of the treatment device 114. A venous blood pressure sensor102 may detect pressure in the venous blood line 137 downstream of thevenous blood pump 104 and upstream of the patient access 122. A freshtreatment fluid pressure sensor 166 indicates the pressure of treatmentfluid downstream of the fresh treatment fluid pump 153 and a wastetreatment fluid pressure sensor 168 indicates the pressure of wastetreatment fluid upstream of the waste treatment fluid pump 154. Thecontroller 240 receives signals from each of the arterial pressuresensor 112, blood inlet pressure sensor 108, blood outlet pressuresensor 106, and venous blood pressure sensor 102, the fresh treatmentfluid pump 153, the waste treatment fluid pump 154, as well as an airdetector 118 that is positioned to detect air in the fresh treatmentfluid line 127. The controller 240 is also connected to control each ofthe arterial blood pump 110, replacement fluid pump 116, thesupplemental fluid pump 142, the supplemental fluid pump 144, the freshtreatment fluid pump 153, and the waste treatment fluid pump 154. Inembodiments, each pump contributing to flow balance may have a pressuresensor upstream of it to ensure that pressure compensated control of itsspeed can be provided. For example, an additional treatment fluid pumppressure sensor 119 shown in FIGS. 1A-1C may be provided here and in anyembodiments as well. In embodiments, pressure sensors used for pressurecompensated speed control are positioned such that they provide areliable and consistent indication of pressure upstream of therespective pump or pumps. Thus, they may be positioned close or at leastsuch that there are no intervening possible interferences such as tubelengths that could become kinked.

The blood treatment system 200 may also differ from a conventionalsystem in having a controllable flow restrictor 161 that is controlledby the controller to regulate flow resistance in the venous blood line137. The controllable flow restrictor 161 may be of any description. Forexample, it may be a progressive valve controlled by a servo or steppermotor. It may be a variable pinch clamp operatively engaged with atubing length. It may be multiple fixed flow restrictors interconnectedby a manifold that has valves to select a particular of the multipleflow restrictors.

In a treatment operation of blood treatment system 200, fresh treatmentfluid pump 153 and waste treatment fluid pump 154 pump in the directionsindicated by the respective arrowhead of each pump symbol, pump at ratescontrolled to balance the flow of blood in the arterial against the flowin the venous such that a net take-off of fluid (ultrafiltration) or anet infusion or ultrafiltration of fluid takes place as calculated bythe controller 240 or per a command received by the controller 240. Theinstantaneous rate of ultrafiltration or infusion may vary during thecourse of a treatment. The controller 240 may be programmed to ensurethat the net level of ultrafiltrate or infused fluid meets a prescribedtarget which may be stored by the controller 240. The pumping speedsrequired to achieve commanded flow rates may be determined by thecontroller 240 using data stored by the controller such as look uptables or formulas. The ratio of flow rate to pump speed (equivalently,the commanded flow rate) may be presented by this stored data toindicate target pump speeds in a relationship between pressuredifference across the pump as well as flow rate; the pump curves. Forexample, in any of the embodiments, a look up table may have cells withpump speeds where columns and rows correspond to the independentvariables of pressure at the pump inlet (or pressure differential acrossthe pump for non-peristaltic pumps) and flow rate. Operating points maybe interpolated or extrapolated for operating conditions that liebetween or outside those corresponding to the cells or the formula orlook-up table may provide interpolated or extrapolated values.

Note that in this or any of the embodiments, including those defined bythe claims, the ratio of commanded pump speed to estimated flow may begiven by a pump curve that is based on inlet pressure rather thanoutlet-inlet pressure difference depending on suitability for the typeof pump used.

Treatment fluid 124 is pumped by fresh treatment fluid pump 128 at apredefined rate stored in the controller, which rate may be selectedresponsively to the blood flow rate or according to prescription. Thereplacement fluid 120 may be pumped at a rate controlled by thecontroller 240 by controlling the rate of replacement fluid pump 116.The supplemental fluid 134 may be pumped at a rate controlled by thecontroller 240 by controlling the pumping rate of supplemental fluidpump 142. The supplemental fluid 132 may be pumped at a rate controlledby the controller 240 by controlling the rate of supplemental fluid pump144. Any combination of the replacement fluid 120, supplemental fluid134, or supplemental fluid 132 may be included, or none of these. Eachmay be included or not along with the respective lines and pumps, inalternative embodiments. Flow control valves may be of any type asindicated above. As before, line 136 is present to indicate that inalternative embodiments, the supplemental fluids may enter the arterialblood line 139 upstream or downstream of the arterial blood pump 110.

Referring now to FIG. 4D, which shows an overview of a method to bedescribed below with reference to FIGS. 4A through 4C, for establishingand maintaining a condition of fluid balance by fresh treatment fluidpump 153 and waste treatment fluid pump 154 during a treatment based onthe measurement of pressures on the treatment device 114 during atreatment. In a first stage S2, the controller determines flow rates andsettings of controllable flow restrictor 161 and arterial blood pump 110that establish a given average blood side pressure in treatment device114. The process loops through a schedule of predefined blood sidepressures each indicated by an average of readings from blood outletpressure sensor 106 and blood inlet pressure sensor 108 Ave Pb and flowrates of waste treatment fluid pump 154 Qb commanded by the controller240. For each combination and flow Qb and pressure Ave Pb, thecontroller 240 determines, through error control, a position ofcontrollable flow restrictor 161 (restrictor setting) that establishesthe given blood side pressure. A function or equivalent is finallygenerated to provide the restrictor setting as a function of Qb and AvePb. This function is then used in a following step S202 to generatefunctions that indicate a command flow rate for fresh treatment fluidpump 153 given a command flow rate of waste treatment fluid pump 154 anda blood side pressure Ave Pb.

At S202, the controller 240 loops through combinations of command flowrates of waste treatment fluid pump 154 and blood side pressures Ave Pband determines a command flow rate of fresh treatment fluid pump 153 atwhich the treatment device 114 blood compartment pressure Ave Pb ismaintained. This condition corresponds to zero convection between theblood and treatment fluid compartments. Any difference between averageblood compartment pressure and average treatment fluid compartmentpressure may be taken as a systematic error in pressure difference. Afunction or equivalent may be fitted to estimate the fresh treatmentfluid pump 153 and error from a given commanded (prescribed, duringtreatment) flow rate of the waste treatment fluid pump 154 (taken as adesired or prescribed treatment fluid flow rate) and measured bloodcompartment pressure Ave Pb for a prescribed blood flow rate during atreatment. This fresh treatment fluid pump 153 rate will then correspondto zero flow in the absence of any oncotic pressure as existed duringthe procedure of S202 using fluids having the same osmotic potentialsuch as the treatment fluid and priming fluid, for example. Note thatboth fluids can be the same fluid for the procedures of S200 and S202.

At S204, a treatment is performed in which the treatment device 114blood compartment is filled with blood. In this case, the pressuredifference between the blood and treatment fluid compartments Ave Pb andAve Ptf are measured and stored to represent a difference caused byoncotic pressure due to the composition of blood. The oncotic pressureand error calculated from the function generated at S202 are used todetermine a balanced flow rate Qtff of the fresh treatment fluid pump153 given prescribed blood and treatment fluid flow rates duringtreatment. The process of flow chart of FIG. 4D summarizes the processesof flow charts 4A through 4C as indicated in each operation S200-S204 ofFIG. 4D.

As shown further below, the of FIG. 4D is used for determining the freshtreatment fluid pump 153 and waste treatment fluid pump 154 flow ratesfor achieving a desired target fluid balance of the patient (net removalor infusion of a volume of fluid) through the maintenance of a targetratio and total displacement of these pumps. The method may be extendedto account for the contribution of other sources of fluid, such asreplacement fluid pump 116.

FIGS. 3B and 4A illustrate a configuration and operation of the bloodtreatment system 200 for determining conditions for the establishment oftarget fluid pressure Pb, typically priming fluid, on the blood side ofthe treatment device 114. Initially, before the establishment of thetreatment fluid no-flow condition illustrated in FIG. 3B, the treatmentfluid compartment of treatment device 114 would be filled in a primingoperation. This may be done in a variety of ways including initiallypumping treatment fluid or priming fluid through the waste treatmentfluid line 125 and fresh treatment fluid line 127 and thereby throughthe treatment device 114. Then the configuration of FIG. 3B isestablished and the procedure of FIG. 4A is performed.

At S22 a command is received, or generated, by the controller 240 tobegin a process for determining combinations of blood pump speedsettings and/or flow restrictor settings selected to produce apredefined schedule of average blood pressure in the treatment device114 during treatment operations which setting permit the establishmentof a desired ultrafiltration rate.

See Table 1 infra. At S24, fresh treatment fluid pump 153 and wastetreatment fluid pump 154 are halted. In further embodiments, thetreatment fluid compartment of the treatment device 114 may be isolated,or further isolated, by closing control valves (not shown) such as pinchclamps, rather than shutting off pumps. In embodiments, the pumps areperistaltic pumps that occlude the line such that they prevent flow whenhalted. The halting of the fresh treatment fluid pump 153 and wastetreatment fluid pump 154 is effective to block flow through, or from,the treatment fluid compartment of the treatment device 114 therebyisolating it except for a membrane of the treatment device. A source ofpriming fluid is connected S26 and the blood pump operated to establisha priming fluid flow in the blood compartment (blood side) of thetreatment fluid device. Preferably priming fluid is provided in acontainer so that a recirculating flow can be established. During thepriming operation, normally incident to the set-up of a blood treatment,a table of treatment fluid flow rates vs pressures is filled out asdescribed below. An example is shown in Table 1. During the priming, thevenous blood line 137 and arterial blood line 139 may be connected topriming fluid source/sink 123 recirculating through a container (notshown separately). The priming fluid can come from an inline source or acontainer for single-pass to a drain. Other arrangements for achievingflowing or recirculating priming fluid in the blood circuit of a bloodtreatment device are known and any of these may be implemented in thepresent embodiment.

TABLE 1 Schedule of flow rates and pressures for estimating restrictorsetting Measured Command Command Measured Restrictor Qb (ml/min) Ave Pb(mmHg) Ave Pb (mmHg) setting 50 100 100.14 AU 50 250 250.59 AU 50 400400.08 AU 200 100 100.89 AU 200 250 251.54 AU 200 400 398.71 AU 400 10098.72 AU 400 250 248.46 AU 400 400 398.15 AU

At S28, after the controller 240 has implemented the above conditions itcontrols the arterial blood pump 110 to a predefined speed (workingthrough each row in the table) and then at S32, modulates the speed ofthe blood pump and the adjustment of controllable flow restrictor 161 toachieve predefined pressure (second column of Table 1) of the primingfluid in the treatment device 114 as indicated by an average of thepressures in the venous blood line 137 and arterial blood line 139: Pbaand Pbv, the average being denoted as Ave Pb. This is done in accordwith a first pressure value in a schedule as illustrated by example inTable 1 (column 2). The regulation proceeds in a feedback controloperation until the target Ave Pb is at least approximately established.The arterial blood pump 110 rate and setting of the controllable flowrestrictor 161 that provides approximates the target predefined pressureon the treatment device 114 blood side (Ave Pb) may be recorded at S34.Also recorded is the actual measured value of the blood side pressureAve Pb and the pumping rate Qb required to achieve that blood sidepressure Ave Pb. The combination of blood pump rate and controllableflow restrictor setting are later used to establish an Ave Pb for thetreatment filter represented in Table 1. The restrictor settings dependon the type of flow restrictor and may be, for example, steps orresistance of an encoder, force, or other unit. After The third throughfifth column is generated, the data may be fit to a function orfunction-equivalent that relates the Ave Pb to the restrictor settingand blood pump flow rate. This process may be done at the beginning of atreatment or it may be performed for each configuration of the treatmentapparatus and provided to the controller for use over multipletreatments.

The targeted set of Ave Pb may be selected to cover a realistic range ofvariability during a treatment when blood is flowing simultaneously withthe treatment fluid. Table 1 shows as an example of such targets (100,250, and 400 mmHg) that is suitable for a dialysis system but notgenerally limiting of the disclosed subject matter. The treatment device114 blood side pressure may be taken by the controller 240 as an averageof the pressures indicated by blood outlet pressure sensor 106 and bloodinlet pressure sensor 108 which the controller 240 may calculate. Theblood side pressure may also be taken as one or the other or someweighted average of the indications of the blood outlet pressure sensor106 and blood inlet pressure sensor 108 which corresponds to a type offilter being used. The controller 240 may predict the arterial bloodpump 110 speed corresponding to fixed target flow rate, vary theresistance or fix the resistance and vary the arterial blood pump 110,or vary both. The procedure repeats at S36 until all the target Pbvalues are established and the pump and restrictor settings determinedand recorded. In the table, three Ave Pb values are generated and thesettings required to achieve them recorded. At S38, a look-up table orformula is generated from the Ave Pb and the pump speed and flowrestrictor settings so that they can be reestablished from the settingsduring a further synchronization operation and during treatment.

Referring now to FIGS. 3C and 4B, at S39 a command is received by thecontroller 240, or generated by it, to develop data that providesfunctions allowing blood treatment system 200 controller 240 to estimatepump settings for treatment. The command initiates the presentprocedure. See Table 2. The blood flow rate Qb and Ave Pb are the sameas the schedule from the first two columns of Table 1. These representtarget blood side flow rate Qb and pressure Ave Pb. The restrictorsetting for each target blood side flow rate Qb and pressure Ave Pb iscalculated from the function calculated at S38. However, the input forthe Ave Pb is the measured input rather than the target. Since thefunction provides a restrictor setting that will provide a given flowrate and blood side pressure, there is no need at this point tofeedback-regulate the restrictor setting to obtain the predefined AvePb. However, in other embodiments, this may be done and the derivationof the function for restrictor setting can be skipped.

Note that although the pressures of the dialysate and blood compartmentare taken to be a combination (such as an average) of the valuesindicated by the pressures at the inlet and outlet pressure sensors forthe respective compartment, it is possible to provide a pressure sensoron the blood treatment device, at least in some embodiments thereof, tomeasure a midpoint pressure directly. In a microtubular fiber-typedialyzer, for example, this could be done for the dialysate side byfitting a pressure measurement pod or tap on the dialyzer housing tomeasure dialyzer compartment pressure, but would be difficult for theblood compartment which is divided among multiple small channels. It isalso possible to employ models of the pressure drop over the length ofthe blood treatment device to obtain a curve of pressure vs.displacement so that the average is a weighted average. Blood pressuremay be taken from the treatment fluid compartment if the oncoticpressure is known. As disclosed herein, at any time, the oncoticpressure may be determined directly so that the controller can store theoncotic pressure and calculate the blood compartment pressure from thetreatment fluid compartment pressure based on the oncotic pressure. Amodel can similarly be used if the convective flow exists between theblood and treatment fluid compartments (e.g., transmembrane flow) toallow the controller to numerically compensate for pressure differencecaused by flow between the blood and treatment fluid compartments.Additionally, in embodiments, the pressure of the blood or treatmentfluid compartment may be taken as one of the respective inlet and outletpressures. This estimate can be refined based on a predefined hydraulicmodel that accounts for the pressure drop within the blood treatmentdevice.

The parameters generated in the method of FIG. 4A and fitting of thefunction at S38 can be done once for multiple treatment cycles as whenthe configurations are the same and therefore the parameters areapplicable to a current treatment cycle. This saves time during thepriming operation at each treatment for the operation of FIG. 4B. At apoint in the priming operation, a treatment apparatus, in priming mode,with the blood circuit filled with priming fluid and connected torecirculate (or otherwise permit the passage of priming fluid throughit), a command is generated at S39 to perform a synchronizationoperation as now described. In S40, the blood circuit is isolated fromthe treatment fluid circuit.

TABLE 2 Schedule of flow rates and pressures for estimating Qtff and TMPerror Pump Pump Cmd Target Calc Measured Measured Calc setting settingQb Ave Pb Restrictor Ave Pb Ave Ptf TMP error Qtff Qtfw (ml/min) (mmHg)setting (mmHg) (mmHg) (mmHg) (ml/min) (ml/min) 50 100 AU 100.00 100.001.48 101.48 100 50 250 AU 249.00 249.00 0.06 249.06 250 50 400 AU 401.00401.00 0.16 401.16 400 200 100 AU 101.00 101.00 1.97 102.97 100 200 250AU 249.00 249.00 −2.39 246.61 250 200 400 AU 401.00 401.00 1.52 402.52400 400 100 AU 100.00 100.00 2.26 102.26 100 400 250 AU 251.00 251.00−2.36 248.64 250 400 400 AU 399.00 399.00 −0.74 398.26 400

At S41, the blood pump and restrictor are controlled to establish an ithAve Pb in the schedule of multiple Ave Pb values. The restrictor 161setting can be established quickly using the function calculated at S38or it can be determined for the current Qb and target (ith) Ave Pb byfeedback control. The latter may take longer which is the advantage offitting the function at S38 at a time prior to treatment and only oncefor multiple treatments. Note also that although the present procedureof FIG. 4B may be done immediately prior to treatment, during a primingstage thereof, it can also be done at other times such that the functiongenerated thereby (See S56 infra) is still valid for use during atreatment. For example, fluid circuit itself may be the same. However,it is advantageous that it be done immediately prior to treatmentbecause wetting the fluid circuits and letting them stand, especially ifportions are compressed by control valves and pumping actuators, maymake the conditions during treatment different from those during thesynchronization process and thereby reduce the applicability of thefunction fit at step S56 during treatment.

The regulating to achieve an actual ith value in the schedule of Ave Pbvalues does not require high precision and an approximation sufficientto ensure that a variety of conditions are obtained and used to fit anestimation function at S56 may be used. A value that is close may bedetermined by comparison of a current measured Ave Pb (indicated by theaverage of blood outlet pressure sensor 106 and blood inlet pressuresensor 108) with a stored range of errors may be used by the controller240 to indicate that the current actual measured Ave Pb is close enoughto the ith value of Ave Pb stored in the schedule. At that point, atS42, the actual Ave Pb determined from the average of (Pbv) blood outletpressure sensor 106 and (Pba) blood inlet pressure sensor 108 may bestored in the data table subsequently to be used for the fitting of apredictive function or function-equivalent. Note that in furtherembodiments, values of the blood inlet and outlet pressures themselvesmay be stored. Also, the average may represent a weighted average ratherthan a simple average that is indicated for the particular type oftreatment device. The sparse data may be fitted to a smooth function toallow estimation of commanded flow rates for conditions duringtreatment. The table of conditions may be stored after reduction to afunction or function-equivalent such as a dense lookup table. They mayalso be stored in unreduced form as) as raw sparse data andextrapolation and/or interpolation for instant conditions interpolationcomputed according to treatment conditions. The table may be sparsematrix, that is, not every cell necessarily has a value.

At S44, an average Ptf (Ave Ptf) is calculated and the differencebetween Ave Pb and Ave Ptf recorded. This difference provides anestimate of systematic error in the TMP that can be used for determiningTMP at other conditions including those during treatment. Now for eachof the original target Ave Pb values the controller has stored ameasured Ave Pb and a measured Ave Ptf as well as an error indicatingthe difference. In embodiments, the error is stored but not the Ave Ptfand in other embodiments, all raw data may be stored including Pba, Pbv,Ptff, Ptfw.

At S45, the fresh treatment fluid pump 153 and waste treatment fluidpump 154 and control valves (again, if present) are set to pump fluidthrough the treatment device 114 as in a treatment. At S46, a jth targetflow rate is established for the waste treatment fluid pump 154 andfresh treatment fluid pump 153 by operating at speeds calculated from astandard conversion (i.e. a predefined ratio of pump speed to expectedflow rate, rather than measured, pressure condition for applying a pumpcurve) to for the jth target flow rate as indicated by example in Table1 (Qtfw flow). At S50, the controller 240 regulates the speed of thefresh treatment fluid pump 153 to bring the current measured Ave Pbtoward the target Ave Pb, recorded at S41, by adjusting the speed of thefresh treatment fluid pump 153. This brings about the synchronization ofthe fresh treatment fluid pump 153 and waste treatment fluid pump 154.In embodiments, a flow through fresh treatment fluid pump 153 isadjusted until synchronization is established, but either pump could becontrolled as the master and the other as the slave. Another alternativeis a combination approach, where both pumps take turns being adjusted toachieve synchronization. The pressure and pump settings identified inTable 1 are recorded at S52. This is repeated by looping through j and iat S54 and S55 until all conditions have been generated and thecorresponding values in Table 1 recorded. Thus, a matrix of combinationsof Ave Pb and Qtfw plus attending data for each combination includingthe Qtff speed, and pressures indicated by fresh treatment fluidpressure sensor 166 (Ptff) and waste treatment fluid pressure sensor 168(Ptfw) are recorded in a data store of the controller 240.

At S56, the data recorded at S44 and S52 may be fitted to a look uptable or fitted to a function to be used for control which maps a givencombination of Ave Pb and Qtfw to an output Qtff and TMP error. Byfitting to a look up table it is meant that values may be interpolatedbetween cells of the table by a fitted curve or surface and a table manymore cells generated to allow rapid use of the fitted data for lookingcombinations of Ave Pb and Qtfw that were not used for the procedure ofFIG. 4B. Calculated values of Ptff and Ptfw may also be yielded by afunction or look up table to provide a validity check on the estimate.That is, the controller 240 may also, or alternatively, generate anerror signal if one or both of the Ptff and Ptfw is beyond a predefinedrange from the output Qtff.

The values of Ptff and Ptfw may provide a mechanism for compensating theinput value of Qtfw and the commanded speed for fresh treatment fluidpump 153, Qtff. The flow rates commanded during treatment based on thefunction derived from Table 2 may adjust for differences between thepressure at the respective inlets of the waste and fresh treatment fluidpumps corresponding to the function and those existing at the time oftreatment when balanced flow is implemented.

During a treatment, given an average blood pressure Ave Pb indicated bythe average of blood outlet pressure sensor 106 and blood inlet pressuresensor 108, for a commanded blood flow rate Qb, and a commandedtreatment fluid flow rate of waste treatment fluid pump 154 Qtfw, aspeed of the fresh treatment fluid pump 153 Qtff is automaticallygenerated which is assured to provide the precise 1:1 flowsynchronization of the fresh treatment fluid pump 153 and wastetreatment fluid pump 154 at those operating conditions. The controller240 then operates the fresh treatment fluid pump 153 at the outputspeed. This speed may be further refined to compensate for differencesbetween the pump inlet pressure conditions when the map of conditionswas created versus the conditions when the function is called upon toestimate the speed of the fresh treatment fluid pump 153. FIG. 4Cprovides the implementation details that further refine this process inorder to provide precise balancing of the Qtff and Qtfw and furtherpermit the implantation of a prescribed ultrafiltration rate.

Referring now to FIGS. 3D and 4C, at S62, a command is received by, orgenerated by, the controller 240 to perform a treatment. During atreatment, blood is pumped by arterial blood pump 110 with freshtreatment fluid pump 153 and waste treatment fluid pump 154 turned off.The treatment fluid circuit may be filled with priming fluid ortreatment fluid at this point which is presumed to be at the beginningof a treatment, however it can be repeated at other times during atreatment in order to reestablish balanced operating conditions for thetreatment fluid pumps.

The treatment fluid no-flow configuration is established at S64. Theprescribed blood flow rate Qb is established by controlling the arterialblood pump 110 at S65. At S66, the Ave Pb is calculated from bloodoutlet pressure sensor 106 and blood inlet pressure sensor 108 andstored. This measured Ave Pb is stored as a target Ave Pb. Next, at S67,the difference between the target Ave Pb and Ave Ptf may be calculatedfrom the blood outlet pressure sensor 106, blood inlet pressure sensor108, fresh treatment fluid pressure sensor 166, and waste treatmentfluid pressure sensor 168 readings. This may be recorded as a measure ofthe oncotic pressure Ponc which biases the transmembrane pressure TMPrelative to the condition where blood and treatment fluid compartmentscontain fluids with the same osmotic potential. As indicated elsewhereherein, the oncotic pressure may be used for a number of functions.Referring now also to FIG. 3E, at S68 the controller 240 selects a speedof the waste treatment fluid pump 154, for example based on a storedprescription entered by an operator or retrieved from an externalsource, such as a patient treatment profile database. At S70, the TMPerror is calculated from the function fitted at S56 of FIG. 4B based onQtfw and target Ave Pb. At S72, the fresh treatment fluid pump 153 speedQtff is calculated based on the function fitted at S56 based on Qtfw andtarget Ave Pb reduced by the TMP error calculated at S70 and the oncoticpressure Ponc calculated at S67. This corrects the estimate of Qtff forthe TMP error and the oncotic pressure caused by the blood. The freshtreatment fluid pump 153 is commanded to the calculated speed Qtff andthe controller 240 at S74 adjusts the speed of fresh treatment fluidpump 153 Qtff such that current measured Ave Pb is restored to theinitial target Ave Pb. Once the fresh treatment fluid pump 153 and oftreatment fluid pump 154 are thus synchronized, the pressure indicatedby waste treatment fluid pressure sensor 168 may then be used at S76 todetermine the flow rate, with compensation based on inlet pressure, andthe speed of the of treatment fluid pump 154 adjusted to provide adesired ultrafiltration rate or infusion rate at S78, as prescribed.Since the speed adjustment may affect the inlet pressure of the of wastetreatment fluid pump 154, the pump compensation may be recalculated, thepump speed adjusted again until it stops changing by looping throughS80. The fresh treatment fluid pump, at any time, may be adjusted inresponse to a measured inlet pressure, for example using a pressuresensor such as 119.

The synchronization process of FIGS. 4B and 4C can run again based onany of a variety of different criteria, automatically, under control ofthe controller. For example, if the blood or treatment fluid flow ratesis/are changed, the ultrafiltration or infusion rate is changed, aperiod of time has elapsed, a component is changed such as a treatmentdevice swap, a change in pressure at any point, access patency change,patient position change, and others.

The measured oncotic pressure may be stored by the controller and usedto provide multiple functions. In embodiments, the oncotic pressure canbe used to estimate a patient's fluid level in order to permit a moreaccurate determination of the required ultrafiltration. The oncoticpressure may be combined with other data to improve the estimate of thepatient's fluid level, for example hematocrit can be measured directly.In embodiments, the controller may be programmed to calculate oncoticpressure at multiple times during a treatment and to combine the oncoticpressure with other data such as hematocrit to generate adjustments to aprescribed ultrafiltration rate that was previously stored in thecontroller. In addition, a predicted and currently estimated—estimatedfrom measured data such as oncotic pressure and hematocrit—fluid levelmay be generated as well. The predicted level may be calculated from theimplemented ultrafiltration rate over time which yields a predictedtotal fluid removed. The controller may alternatively or further beprogrammed to generate a signal indicating a mismatch between aprescribed ultrafiltration rate and a current fluid level of the patientwith accounting for the remaining time left in a treatment. Here, we usethe term oncotic pressure to refer to the pressure difference due to allthe differences in the compositions of the blood and treatment fluidincluding proteins, middle molecules, electrolytes, and any othercomponents that may contribute to diffusion potential.

In any of the embodiments where blood side pressure of the bloodtreatment device is used as a target to bring the fresh treatment fluidpump to represent a state of zero ultrafiltration (equivalently, zerotransmembrane flow or zero transmembrane pressure), in furtherembodiments, the non-blood side pressure of the treatment device mayinstead be stored and used in the same manner. That is Ave Pb may bereplaced with Ave Ptf may for purposes of characterizing the zeroultrafiltration condition. This does not include the measurement ofoncotic pressure or TMP error. It has been determined that feedbackcontrolling to achieve a target Ave Ptf to achieve synchronizationconverges more rapidly, under certain conditions and in certain types ofsystems, than feedback controlling on Ave Pb.

FIG. 5 shows a flow meter 170 that can be used as a reference forsynchronizing pumps to a common flow rate standard. A tube segment 184that is manufactured to precise tolerances and has a known volume andlength is positioned in the waste treatment fluid line 125. An air line188 is connected to a source of pressurized air 190 and furtherconnected to the waste treatment fluid line 125 through a control valve186 connected to be controlled by a controller 195. The controller 195injects a predefined bolus or air into the waste treatment fluid line125 which is carried past two optical sensors 180 and 182 arranged inseries. The optical sensors detect the bolus of air and convey thesignals to the controller 195 which calculates a time difference—atime-of-flight. With the predefined length and diameter of the tubesegment 184, plus the known characteristics of fully developed flow forthe fluid therein, the controller 195 can calculate a volume flow rate.Since the fluid carried by waste treatment fluid line 125 is disposed ofto a drain 126, there is no detriment injecting air into the wastetreatment fluid line 125. Such a flow measurement device, or some other,may be employed advantageously to provide a further estimate of the flowrates on which the pump pressure compensations are based. In addition,an indication of absolute flow rate of a pump may be used by thecontroller to detect an anomalous state of the system and therefore apotential source of error in the flow synchronization mechanismsemployed to achieve balance. The flow rate of a single pump, forinstance the waste treatment fluid pump, may be sufficient since thesynchronization process accurately

FIGS. 6A and 6B show a blood treatment system 300 in which freshtreatment fluid pump 153 and treatment fluid pump 154 are synchronized,to provide a control parameter that can be used as a basis for fluidflow balance. To do so, a synchronization operation is performed as inother embodiments, but in this case, it is done without establishing afixed volume flow through the treatment device 114 as in the embodimentsdiscussed above, for example as described with reference to FIGS. 1A-1E.As will be observed, a series flow of treatment fluid is established inthe treatment fluid circuit without a need to block flow in the bloodcircuit. In the blood treatment system 100, the flow of treatment fluidwas blocked to form a fixed volume channel between the blood pumpsthrough the blood treatment device 114. Here, instead, a directconnection between the treatment fluid pumps is established by closingthe circuit on the source/sink side of the treatment fluid circuit. Infirst embodiments, the volume of the direction connection channel isfixed and pressure is measured to indicate a mismatch in the pumpingrates. In second embodiments, a level of treatment fluid volume in anaccumulator provides in indication of flow mismatch. The approach ofclosing the fluid circuit on the source/sink side of the treatment fluidcircuit may be advantageous for a variety of reasons not least of whichis that it avoids halting flow in the blood circuit which reduce therisk of blood clotting. During priming or during treatment, to implementa synchronization operation, a closed loop is temporarily formed tocirculate treatment fluid and the net uptake or loss of fluid into theclosed loop, which represents fluid passing through the treatment device114 into the closed loop, is detected and the pumps regulated to bringthe net rate of uptake or loss to zero, thereby synchronizing the freshtreatment fluid pump 153 and of treatment fluid pump 154. The detectionof net uptake or loss may be accomplished by measuring pressure in theclosed loop with a pressure measurement device or pressure sensor (suchas a pressure transducer) 312 or by measuring the weight gain of a fluidaccumulator 310 (also referred to as an accumulator) in the loop using ascale 301. Instead of a scale, a level indicator in a fixed volumechamber may be used as will be evident from the further descriptionbelow.

FIG. 6A shows a flow a blood treatment system 300 that regulates theflow of treatment fluid to generate a cumulative target ratio of fluiddrawn or infused into a patient over the course of a treatment. A bloodtreatment system 300 regulates the flow of fluid in a fluid circuit 321that includes an arterial blood line 139, a venous blood line 137, afresh treatment fluid line 127 and a waste treatment fluid line 125. Thenet flow of fluid into or out of a patient, at any given time, isdetermined by a then-instant difference between the volume of treatmentfluid pumped from a treatment device 114 to the combined volume pumpedinto the both the treatment device 114 and the blood lines. Blood ispumped from a patient 122 (conventionally, via a patient access) intothe treatment device 114 by an arterial blood pump 110 and flows fromthe treatment device 114 back to the patient 122. The illustratedconfiguration is common for dialysis systems, and may include all thetypical incidents thereof, but differs specifically in that there aretwo treatment fluid pumps: a fresh treatment fluid pump 153, which pumpsfresh treatment fluid 124 into the treatment device 114, and a wastetreatment fluid pump 154, which pumps waste (spent) treatment fluid fromthe treatment device 114 to a drain 126. Control and sensing areprovided by a controller 340 which may be of any form but typically aprogrammable digital controller; an embedded computer. Treatment fluid124 is pumped from a source through an air detector 118 through thetreatment device 114, to the drain 126 (indicated by W for waste).

A replacement fluid 120 may be pumped into the arterial blood line 139or the venous blood line 137 through a replacement fluid line 135 or138, respectively (or both) for predilution, post-dilution. Inalternative embodiments, the dilution may occur at a midpoint of thetreatment device 114, for example by splitting the treatment device 114into two parts and providing a junction between them. The treatmentdevice 114 may be adapted for any type of blood treatment including, butnot limited to, dialysis, hemofiltration, hemodiafiltration, apheresis,adsorption, hemoperfusion, and blood oxygenation. Further supplementalfluids indicated by supplemental fluid 134 and supplemental fluid 132may be pumped into the arterial blood line 139 by respective pumps,namely, supplemental fluid pump 142 and supplemental fluid pump 144,either or both of which may be present. Examples of supplemental fluidsare drugs and anticoagulant (e.g., citrate, heparin).

Pressure sensors may be provided at various points throughout the fluidcircuit 121. In particular, an arterial pressure sensor 112 may detectpressure of the blood in the arterial blood line 139 upstream of thearterial blood pump 110. A blood inlet pressure sensor 108 may detectpressure of the blood in the arterial blood line 139 downstream of thearterial blood pump 110 and upstream of the treatment device 114. Ablood outlet pressure sensor 106 may detect pressure of the blood in thevenous blood line 137 upstream of the venous blood pump 104 anddownstream of the treatment device 114. A venous blood pressure sensor102 may detect pressure in the venous blood line 137 downstream of thevenous blood pump 104 and upstream of the patient access 122. An inlettreatment fluid pressure sensor 166 indicates the pressure of treatmentfluid downstream of the fresh treatment fluid pump 153 and a wastetreatment fluid pressure sensor 168. The controller 340 receives signalsfrom each of the arterial pressure sensor 112, blood inlet pressuresensor 108, blood outlet pressure sensor 106, and venous blood pressuresensor 102, the fresh treatment fluid pump 153, the waste treatmentfluid pump 154, as well as an air detector 118 that is positioned todetect air in the fresh treatment fluid line 127. The controller 340 isalso connected to control each of the arterial blood pump 110,replacement fluid pump 116, the supplemental fluid pump 142, thesupplemental fluid pump 144, the fresh treatment fluid pump 153, and thewaste treatment fluid pump 154.

The blood treatment system 200 also differs from a conventional systemin having a treatment fluid branch loop closer 320 that includes anoutgoing loop line 316 and an incoming loop line 318, either anaccumulator 310 weighed by the scale 301, or a pressure measurementdevice 312, as well as a loop control valve 302, a fresh treatment fluidcontrol valve 304 and a waste treatment fluid control valve 306. In FIG.6A, the loop control valve 302, the fresh treatment fluid control valve304 and the waste treatment fluid control valve 306 are set in atreatment mode to allow fresh treatment fluid to circulate through thetreatment device 114 and to permit waste treatment fluid to pass to thedrain 126. The treatment fluid branch loop closer 320 is not in the loopas determined by the closed position of the waste treatment fluidcontrol valve 306. Thus, fluid passes directly from the treatment fluid124 to the drain 126 by way of the treatment device 114 and the freshtreatment fluid pump 153 and waste treatment fluid pump 154. Instead ofa scale 301 a fluid level detector may be used to indicate changes influid volume of the accumulator 310.

In a synchronization mode shown in FIG. 6A, the treatment fluid source124 and the drain 126 are cut off by the closed positions of freshtreatment fluid control valve 304 and waste treatment fluid controlvalve 306. The open position of 6A, the loop control valve 302 causes aclosed loop to be formed by the venous blood line 137, arterial bloodline 139, outgoing loop line 316, accumulator 310, and the incoming loopline 318. In the alternative embodiment, the loop includes the pressuremeasurement device 312 instead of the accumulator 310. When the freshtreatment fluid pump 153 and waste treatment fluid pump 154 are out ofsynch, the scale 301 or the pressure sensor 312 will indicate a rise orfall in weight or pressure over time and the controller 340 changes oneof the fresh treatment fluid pump 153 and waste treatment fluid pump 154into synch. The data converting pump flow to pump speed can thereby beadjusted so that fluid balance is better maintained during treatment.

In a treatment operation of blood treatment system 300, fresh treatmentfluid pump 153 and waste treatment fluid pump 154 pump in the directionsindicated by the respective arrowhead of each pump symbol, pump at ratescontrolled to balance the flow of treatment fluid in the fresh treatmentfluid line 127 against the flow of blood in the venous blood line wastetreatment fluid line 125 such that a net take-off of fluid(ultrafiltration) or a net infusion of fluid takes place as calculatedby the controller 340 or per a command received by the controller 240.The instantaneous rate of ultrafiltration or infusion may vary duringthe course of a treatment.

The controller 340 may be programmed to ensure that the net level ofultrafiltrate or infused fluid meets a prescribed target which may bestored by the controller 340. The pumping speeds required to achievebalanced flow rates may be determined by the controller 340 using datastored by the controller such as look up tables or formulas. These dataare generated using the synchronization procedures of the variousembodiments and optionally by using pump curve data as well. The ratioof flow rate to pump speed may be presented by this stored data toindicate target pump speeds (or, equivalently, commanded flow rates) ina relationship between pressure difference as well as flow rate. Forexample, in any of the embodiments, a look up table may have cells withpump speeds where columns and rows correspond to the independentvariables of pressure at the pump inlet (or pressure differential acrossthe pump for non-peristaltic pumps) and flow rate.

At the same time treatment fluid 124 is pumped by fresh treatment fluidpump 128 at a predefined rate stored in the controller, which rate maybe selected to correspond to the blood flow rate. The replacement fluid120 may be controlled by the controller 340 which determines the rate ofreplacement fluid pump 116. The supplemental fluid 134 may be pumped ata rate regulated by the controller 340 by controlling the pumping rateof supplemental fluid pump 142. The supplemental fluid 132 may be pumpedat a rate controlled by the controller 340 by controlling the rate ofsupplemental fluid pump 144. Any of the replacement fluid 120,supplemental fluid 134, or supplemental fluid 132 may or may not beincluded, along with the respective lines and pumps, in alternativeembodiments. Flow control valves may be of any type as indicated above.As before, line 136 is present to indicate that in alternativeembodiments, the supplemental fluids may enter the arterial blood line139 upstream or downstream of the arterial blood pump 110.

Referring to FIG. 6B, in additional embodiments, a bridge line 147 thatcan be opened or closed selectively by the controller 340, connects thereplacement fluid line 143 and the waste treatment fluid line 125. Thismay be controlled by means of a control valve 145. Another bridge line117 that can be opened or closed selectively by the controller 340,connects the replacement fluid inlet line 149 and the waste treatmentfluid line 125. This may be controlled by means of a control valve 115.Thus waste treatment fluid pump 154 and supplemental fluid pump 142 maybe connected in series through treatment fluid branch loop closer 320.This allows the supplemental fluid pump 142 to be synchronized againstthe waste treatment fluid pump 154 by selected actuation of the controlvalves, e.g., 115, 145, 304, as will be evident from inspection. Inalternative embodiments, any of the non-blood pumps may be synchronizedwith any other non-blood pump in the same manner using the same orsimilar devices.

Referring to FIG. 7 , a blood treatment system 400 is illustratedschematically with some key elements of certain embodiments of thedisclosed subject matter. A treatment device has a membrane 407 thatdivides blood 401 and non-blood 403 compartments. The blood compartment401 may include the composite volume of the internal lumens of amicrofiber bundle and the non-blood compartment 403 may be net spaceoutside of such a microfiber bundle confined by a housing. A blood pump412 pumps priming fluid or blood into the blood compartment 401 and avariable restrictor 402 restricts the flow of priming fluid to permitthe pressure in the blood compartment 401 to be adjusted selectively bya controller 420. In treatment mode, the variable restrictor is notused. The controller 420 controls the speeds of pumps and detects thepressures of the blood 401 and non-blood 403 compartments by means ofpressure sensors 406 and 408, which are shown schematically but mayrepresent inlet and outlet pressure sensors for each compartment as inthe foregoing embodiments. Net fluid transfer to/from the non-bloodcompartment is controlled by regulating the relative speeds of fresh 404and waste 410 treatment fluid pumps. Flow meters 170 as described withreference to FIG. 5 may be provided on one or both of the fresh 418 andwaste 419 treatment fluid lines. Since in the embodiment of FIG. 5 , airis injected in the fluid traversing the flow meter 170, an air removalfilter 171 may be provided in the fresh treatment fluid line 418downstream of the flow meter 170. The flow meter 170 may be used as aconfirmation of the synchronization procedure of the embodiments. If acontroller 420 detects a disagreement between the flow rates whensynchronization is established (e.g., S74, S108), then the controller420 may generate a signal indicating the disagreement. The signal may beused to generate an alert or alarm condition.

FIG. 8 shows a spot method for synchronizing fresh and waste treatmentfluid pumps during a treatment, according to embodiments of thedisclosed subject matter. In this method the treatment fluid pumps aresynchronized for the then-current set of conditions in a treatmentphase. This is similar to the procedures of FIGS. 4B and 4C except thatinstead of mapping a number of conditions of Ave Pb and Qtfw to estimateQtff, a single Ave Pb (or as discussed above, a single Ave Ptf mayapply) is measured, with no treatment fluid flow, from the currentoperating conditions and stored as a target and used with thecurrent—prescribed—Qtf to determine a synchronous speed for the freshtreatment fluid pump. This is then offset to achieve ultrafiltration andrefined by regulating the waste treatment fluid pump to achieve inletpressure compensation. This has the benefit of determining thesynchronous speed of the fresh treatment fluid pump for the preciseconditions for treatment.

In the procedure of FIG. 8 , a procedure for spot synchronization is nowdisclosed in further detail. instead of deriving a function to estimatefresh treatment fluid pumping rate from waste treatment fluid pumpingrate and average blood compartment pressure, the fresh treatment fluidpumping rate is determined for a current, or predefined combination ofwaste treatment fluid flow rate and blood compartment average pressure.This can also be done as a complement to the derivation of an estimationfunction. For example, an operator may command the system to perform asingle operating-point synchronization. At S100, during or before atreatment, a command is received or generated by the controller toresynchronize the treatment fluid pumps. At S102, the treatment fluidpumps are halted establishing a zero transmembrane pressure while theblood pump keeps running (or is started). At S104, with the blood pumprunning at a prescribed rate, the blood compartment average pressure AvePb (or Ave Ptf) is measured and stored as a target. Then the prescribedtreatment fluid flow rate is established by commanding the wastetreatment fluid pump at S106. The fresh treatment fluid pump is thencontrolled until the target blood compartment average pressure isrestored at S108. At S109, the ultrafiltration is established bystepping the waste treatment fluid pumping rate up and iterativelycompensating based on the measured inlet pressure to the waste treatmentfluid pump. At S110, the treatment fluid pumping rates having beenprecisely established for the current blood flow rate, the treatmentresumes at S110. At S112, if, during treatment, there is a change inaverage blood compartment pressure, the controller may command that theforegoing operation be repeated otherwise treatment continues at S110.

It will be observed that FIG. 8 illustrates a method for controllingflow in a fluid circuit. In the method, a controller regulates the flowof fluid across a blood treatment device membrane contacting a bloodflow path responsively to a pressure signal indicating pressure in theblood treatment device. The regulating includes controlling speeds ofinflow and outflow pumps, the inflow pump pumping treatment fluid intothe blood treatment device and the outflow pump pumping treatment fluidout of the blood treatment device responsively to a target pressureindicating a blood and/or treatment fluid side of the membrane. At asynchronization time prior to the regulating, the target pressure isobtained and stored in a data store of the controller. The targetpressure is calculated from a detected pressure on the blood and/ortreatment fluid side of the membrane at a time when the inflow andoutflow pumps are halted. The controller, at the synchronization time,halts the inflow and outflow pumps.

The regulating operation may be followed by, or include, advancing thedownstream synchronized pump speed to provide a prescribed or calculatedultrafiltration rate such that a target net ultrafiltered volume isremoved from a patient by the end of the treatment. The advancing may beaccomplished simply by increasing the flow rate of the downstream pumpby an amount equal to the targeted ultrafiltration rate. So if thecommanded flow rate of the effluent pump is 100 ml/min and theultrafiltration rate is 5 ml/min, then the advanced effluent pump ratewill be changed from the value 100 ml/min, at which the synchronizationwas performed, to 105 ml/min.

The target pressure may be obtained from the blood side of the treatmentdevice or from the treatment fluid side of the treatment device,respectively, by averaging inlet and outlet pressures on the respectiveside. Alternatively, the pressure may be obtained from the treatmentfluid (non-blood) side outlet only. The foregoing method embodiment maybe performed during priming and repeated during treatment.

In any embodiments, the pressure sensor may be located on the downstreamnon-blood side of the treatment device and the pressure sensor may beused alone for synchronization. Alternatively, pressure sensors onnon-blood inlet and outlet may be averaged for purposes ofsynchronization. In yet additional embodiments, a pressure sensor mayform part of the blood treatment device and indicate a temperature at amiddle point, the inlet, or the outlet of the non-blood compartment ofthe blood treatment device. In any embodiments, the pressure sensor maybe located on the downstream blood side of the treatment device and thepressure sensor may be used alone for synchronization. Alternatively,pressure sensors on blood inlet and outlet may be averaged for purposesof synchronization. In yet additional embodiments, a pressure sensor mayform part of the blood treatment device and indicate a temperature at amiddle point, the inlet, or the outlet of the blood compartment of theblood treatment device.

FIG. 9 shows a programmable control system with details that may beinherent in any of the controller embodiments disclosed herein. Aprocessor 10 receives signals from sensors 14, optionally by way of oneor more signal conditioners represented collectively at 18. Examples ofsignal conditioners will be evident from the embodiments, but mayinclude analog filters to more complex devices such as machine learningprocessors that classify diffuse signal combinations. The processor maystore and receive data to and from a data store 12 or a network/Internet20. Actuators 16 represent the various actuators described herein. Theprocessor may connected for interaction with users via one or more userinterface 22 elements such as buttons, screens, keyboard, pointingdevices, alarm annunciators, speakers, lights, etc.

FIGS. 10A and 10B show a figurative representation of a blood treatmentdevice 512 with blood compartment 510 and non-blood compartment 511separated by a membrane 520. In FIG. 10A, the fluid balance of a patientis controlled by a controller (not shown) by regulating the relativespeeds of treatment fluid pumps 506 and 514. In FIG. 10B, the fluidbalance of a patient is controlled by a controller (not shown) byregulating the relative speeds of blood pumps 502 and 504. Thesynchronization procedure of FIG. 8 may be used to obtain a speed of thetreatment fluid pump 506 that is synchronized to the speed of the pump514 by determining a target pressure of the non-blood compartment 511 atwhich there is no flow through the membrane and synchronizing findingthe speed of the pump 506 that achieves that target pressure for thedesired pumping rate of the pump 514. However, a similar procedure canalso be used when blood flow is balanced instead of treatment fluid asin the embodiment of FIG. 10B by determining the speed of the blood pump504 that is synchronized with the blood pump 502 based on a targetpressure obtained by establishing the no-transmembrane flow conditionduring priming. The target pressure may be obtained by halting flow ofpriming fluid or blood by halting both blood pumps 502 and 504. Then,the pressure while there is treatment fluid flowing through thenon-blood compartment may be measured. The pressure may be any of thedisclosed embodiments including the average of the blood inlet andoutlet pressures. Then the blood pump 502 can set to a predeterminedflow rate and the pump 504 operated to determine a synchronized speed ofthe blood pump 504 for a selected speed of the blood pump 502. Note that516 indicates one or more pressures sensors which may be any of thoselisted as alternatives including average of inlet and outlet pressure.

Referring to FIG. 11 , a multiple fluid blood treatment system 500includes a fluid circuit 505 and a machine 550. The system 500 iscapable of hemofiltration, hemodialysis, and hemodiafiltration. Themachine 550 regulates the flow of treatment fluid to generate acumulative target ratio of fluid drawn or infused into a patient 122over the course of a treatment. The blood treatment system 500 regulatesthe flow of fluid in a fluid circuit 505 that includes an arterial bloodline 585, a venous blood line 586, a fresh treatment fluid line 536 anda waste treatment fluid line 537. The net flow of fluid into or out of apatient or priming source/sink, at any given time, is determined by acurrent difference between the volume of treatment fluid pumped from atreatment device 114 to the combined volume pumped into the treatmentdevice 114 and pumped into the arterial blood line 585, a venous bloodline 586. Fluid (blood or priming fluid) is pumped from a source (e.g.,patient 122 or priming fluid source/sink 123) into the treatment device114 by a blood pump 563 and flows from the treatment device 114 back tothe patient 122 or priming fluid source/sink 123, which may be a drain,collection container, or recirculating container. The illustratedconfiguration may include typical incidents of dialysis machines such asdetachable fluid circuits, peristaltic pumps, sensors, etc. In thiscase, flow balance to achieve the desired ultrafiltration is provided byregulating the rates of fluid pumps including two treatment fluid pumps:a fresh treatment fluid pump (also referred to as a dialysate pump) 573,which pumps fresh treatment fluid 124 into the treatment device 114, awaste treatment fluid pump (also referred to as an effluent pump) 574,which pumps waste (spent) treatment fluid from the treatment device 114to a drain 126, a supplemental fluid pump 541, which pumps a supplement,such as an anticoagulant, from a supplemental fluid source 132 into thearterial blood line 585, and replacement fluid pumps 540 and 542, whichpump a first replacement fluid 120 and a second replacement fluid 133,respectively, into the arterial blood line 585 at the locationstherealong indicated in the drawing. Note that other fluids can be addedor substituted according to the requirements of different treatmentmodalities and the illustrated examples are not intended to be limiting.

As above, control and sensing are provided by a controller 240 which maybe of any form and again, typically, a programmable digital controllersuch as an embedded computer. Treatment fluid is pumped from a treatmentfluid source 124, such as a bag or fluid proportioning system, by afresh treatment fluid pump 573. The treatment fluid passes through awarmer 592, an air detector 579, through or past temperature andpressure measurement devices P in1, T in1 569, through or past pressuremeasurement devices P out1 570 and into the treatment device 114. Beforeentering the treatment device 114 the fresh treatment fluid line 536passes a clamp PC1 571 (though a fluid control valve may also be used)that is controlled by the controller 240. The treatment fluid flowsthrough the treatment device 114 pumped by an effluent pump (FP3) 574.The treatment fluid flowing from the treatment device 114 and passes toa drain (or collection chamber) 126. The waste line 537 from thetreatment device 114 engages with a clamp DC that is controlled by thecontroller 240. The waste line 537 also passes an effluent pressuresensor EP 575 upstream of the effluent pump (FP3) 574. The waste line537 also passes a waste pressure sensor WBP 576 downstream of theeffluent pump (FP3) 574. The waste line 537 also passes a blood detector580 and a free hemoglobin sensor 577. Flow in the waste line 537 iscontrolled by a clamp DC 581 (though a fluid control valve may also beused) between a junction 547 and the treatment device 114 and a wasteclamp WC 578 between the waste outlet and the effluent pump (FP3) 574.

A replacement fluid RF1 120 may be pumped into the arterial blood line585 (or alternatively or in addition into the venous blood line venousblood line 586) through a replacement fluid line 593. In alternativeembodiments, the dilution by a replacement fluid may occur at a midpointof the treatment device 114 as discussed above. The replacement fluidRF1 120 is pumped by a pump 542 through a line 593 which passes throughan air sensor Air2, an upstream pressure sensor P in2 560, a downstreampressure sensor P out2 and temperature sensor T out2 555, and a pinchclamp PC2 554. The replacement fluid passes through a sterile filter 583before it flows into the arterial blood line 585.

A replacement fluid RF2 133 may be pumped into the arterial blood line585 (or alternatively or in addition into the venous blood line venousblood line 586) through a replacement fluid line 594. In alternativeembodiments, the dilution by the replacement fluid may occur at amidpoint of the treatment device 114 as discussed above. The replacementfluid RF2 133 is pumped by a pump 540 through line 594 which passesthrough an air sensor Air4, an upstream pressure sensor P in4 552, adownstream pressure sensor P out4 and temperature sensor T out4 557, anda pinch clamp PC4 556.

A supplemental fluid (such as an anticoagulant) 132 may be pumped intothe arterial blood line 585 (or alternatively or in addition into thevenous blood line venous blood line 586) through an anticoagulant line595. The supplemental fluid 132 is pumped by a pump 541 through line 595which passes through an air sensor Air5, a pressure sensor P out5 559and a pinch clamp PC5 558.

Blood is pumped by a blood pump BP 563 through air sensors ADAc and ADAx567 which are a sensitive air bubble detectors connected to independentalarm systems for safety. The arterial blood also passes an inletpressure sensor AP 568 and an outlet pressure sensor APF 564 multiplecontaminant detector (air or non-blood fluid) BDA 565. Venous bloodreturns from the treatment device 114 via venous blood line 586. Avenous line clamp 562 blocks returning blood if a safety hazard isdetected, such as air in the blood lines. A an air detector BDV 566 is asensitive air detector for indicating the presence of bubbles in thevenous line.

A bypass line 591 is used for synchronizing the flow of replacementfluid pump FP2 542 with the effluent pump FP3 574. The bypass line 591is opened and closed by means of a clamp BPC 572 (though a fluid controlvalve may also be used). The bypass line 591 connects the replacementfluid RF1 line 593 with the waste line 537.

The treatment device 114 may be adapted for any type of blood treatmentincluding, but not limited to, dialysis, hemofiltration,hemodiafiltration, apheresis, adsorption, and hemoperfusion. Further thefluids 132, 133, 120, 124 may be any type of fluid and the typesdescribed are examples not intended to limit the disclosed subjectmatter. Examples of fluids are medicaments, drugs, and anticoagulant(e.g., citrate, heparin).

The controller 240 is also connected to control each of the blood pump563, replacement fluid pump 542, replacement fluid pump 540, thesupplemental fluid pump 541, the fresh treatment fluid pump 573, and thewaste treatment fluid pump 574. In embodiments, each pump contributingto flow balance may have a pressure sensor upstream of it to ensure thatpressure compensated control of its speed can be provided. This is thecase in the illustrated example. In embodiments, pressure sensors areused for pressure-compensated speed control. They may be positioned suchthat they provide a reliable and consistent indication of pressureupstream of the respective pump or pumps.

In a treatment operation of blood treatment system 500, the pumps pumpfluids in the directions indicated by the arrowheads of each pumpsymbol. The controller regulates the speeds to effect a flow balance offluid to/from the patient that meets a target ultrafiltration requiredover the course of the treatment. The system can also control the rateof ultrafiltration within a target range as well. the flow of treatmentfluid in the fresh treatment fluid line 127 against the flow of blood inthe venous blood line waste treatment fluid line 125 such that a nettake-off of fluid (ultrafiltration) or a net infusion of fluid takesplace as calculated by the controller 240 or per a command received bythe controller 240. The instantaneous rate of ultrafiltration orinfusion may vary during the course of a treatment. The controller 240may be programmed to ensure that the net level of ultrafiltrate orinfused fluid meets a prescribed target which may be stored by thecontroller 240. The pumping speeds required to achieve commanded flowrates may be determined by the controller 240 using data stored by thecontroller such as look up tables or formulas. The ratio of flow rate topump speed (equivalently, the commanded flow rate) may be presented bythis stored data to indicate target pump speeds in a relationshipbetween pressure difference across the pump as well as flow rate; thepump curves. For example, in any of the embodiments, a look up table mayhave cells with pump speeds where columns and rows correspond to theindependent variables of pressure at the pump inlet (or pressuredifferential across the pump for non-peristaltic pumps) and flow rate.Operating points may be interpolated or extrapolated for operatingconditions that lie between or outside those corresponding to the cellsor the formula or look-up table may provide interpolated or extrapolatedvalues.

A procedure in which the embodiment of FIG. 11 is used for performinghemofiltration is now described. In FIGS. 12A-12G, the thicker linesindicate lines where a flow is established and the thin lines indicateno-flow. Also, closed clamps are indicated by circles with a lineperpendicular the controlled line when closed parallel to it whenopened. Referring now to FIG. 12A, a simplified version of the drawingof FIG. 11 is shown in an operating mode in which blood is pumped, at adesired blood flow rate, through the treatment device 114 by the bloodpump 563. The other pumps are halted. The clamp DC 581 is open and otherclamps 571, 572, and 554. Clamp WC 578 may have no effect because theeffluent pump 574 is halted preventing any flow through the waste line.Since there is a flow passage between the non-blood compartment of thetreatment device 114 and the effluent pressure sensor EP 575, and sincethere is no flow in the non-blood compartment of the treatment device114 and no flow through the membrane to the blood compartment owing tothe fact that the clamps 571, 572, and 554 are closed and effluent pump574 is halted, the effluent pressure sensor EP 575 indicates thepressure of the non-blood compartment of the treatment device 114 whichalso reflects the average pressure in the blood compartment. Theeffluent pressure is recorded as a target (EP-target) by the controllerin the operating mode shown in FIG. 12A and then the controllerimplements the configuration of FIG. 12B.

In FIG. 12B, the bypass branch clamp 572 and the waste clamp 578 areopened and the clamp 581 is closed. This connects the replacement fluidpump 542 and the and effluent pump 574 in series. The effluent pump 574and the replacement fluid pump 542 are commanded to run at a predefinedreplacement fluid pump rate according to a hemofiltration prescription.That is, the rate of both pumps is set to the rate at which replacementfluid is planned to be infused into the patient blood line. Thereplacement fluid pump 542 is then adjusted while monitoring theeffluent pressure from effluent pressure sensor EP 575 so that thepressure indicated by the pressure sensor EP 575 is equal to the target(EP-target). The commanded rate of the replacement fluid pump 542 thatprovides this target pressure is recorded as a target (Q-sync) commandedflow rate of the replacement fluid pump 542. Next the controllerconfigures the system as shown in FIG. 12C.

Referring to FIG. 12C, in a hemofiltration treatment, the replacementfluid pump 542 is set to the target Q-sync. The effluent pump isoperated at the predefined replacement pump speed used for synchronizingin the procedures discussed with regard to FIG. 12B. Immediatelythereafter, the pressure compensation is used to maintain the speed ofthe effluent pump. As a result, if the pressure indicated by thepressure sensor EP 575 falls, the speed of the effluent pump 574 isincreased and vice versa.

Note that the configuration of FIGS. 12A-12C was identified as asimplified view of the system of FIG. 11 . However, it should be clearthat the configuration of FIGS. 12A-12C is consistent with otherembodiments that include other elements or a bare minimum or equivalentof those shown in alternative embodiments.

A procedure in which the embodiment of FIG. 11 is used for performinghemodiafiltration is now described. Referring to FIG. 12D, the sameprocedure as discussed above for obtaining record the effluent pressureas a target (EP-target) is performed except that both EP and an averageof Pout1 549 and WP (the latter average equal to an average pressure ofthe non-blood compartment, HD avg) are recorded as respective targetpressures. The same configuration is established by the controller as inFIG. 12A except that the clamp 571 (PC1) is opened to permit the sensorPout1 549 to detect the non-blood compartment pressure. Next, after theEP-target is recorded, the controller implements the configuration ofFIG. 12E.

In FIG. 12E, the dialysate clamp 571 is opened and the dialysate pump573 and the effluent pump 574 are commanded to a speed equal to aprescribed dialysate flow rate for the treatment to be performed. Thedialysate pump 573 is commanded by the controller to vary its speedwhile sampling the effluent pressure 575 to determine the commanded flowrate of the dialysate pump 573 that coincides with a measured HD-avgequal to the HD-avg-target as indicated by the effluent pressure EPsensor 575 and the Pout1 549 pressure sensor. As should be clear fromthe present disclosure, the commanded flow rate may be generated from adynamic model such as a curve fit of the pressure data or it may beobtained from the pump rate after the synchronization feedback (PID)control has reached equilibrium or synchronous flow lock of thedialysate pump 573 and the effluent pump 574. In embodiments, thedialysate pump 573 is feedback-controlled based on the error, (effluentpressure HD-Avg)—(HD-Avg-target) so that the dialysate pump 573 runs ata speed that maintains the effluent pressure indicated by the measuredHD-avg. This establishes a command speed of dialysate pump 573Q-Dialysate-sync that is flow-synchronized with the command speed of theeffluent pump 574. The command speed of the dialysate pump is recorded.

In FIG. 12F, the bypass branch clamp 572 is opened and the clamp 581 isclosed. The dialysate pump 573 is halted and PC1 clamp 571 closed. Theillustrated configuration connects the replacement fluid pump 542 andthe effluent pump 574 in series as in FIG. 12B. The same procedure isperformed as described with reference to FIG. 12B to obtain thecommanded rate of the replacement fluid pump 542 that provides thetarget pressure. This commanded rate at synchronization is recorded as atarget (RF-Q-sync). This is a commanded flow rate of the replacementfluid pump 542 that will be used during treatment. Next the controllerconfigures the system as shown in FIG. 12G.

Referring to FIG. 12G, the dialysate line clamp 571 is next opened andthe dialysate pump operated at the speed Q-dialysate-sync. The effluentpump 574 is commanded to a rate equal to the commanded dialysate flowrate used during synchronization procedure of FIG. 12F plus thehemofiltration rate. Then the replacement fluid pump 542 is commanded torun at RF-Q-sync. The controller then implements pressure compensationof the effluent pump 574. The controller may also implement pressurecompensation control of all the pumps as inlet pressure conditions(and/or other conditions) depart from the conditions at the time ofsynchronization. In this mode, hemodiafiltration treatment is performed.

Note that in a variation of the embodiments of FIGS. 12D-12F, thereplacement fluid is not used and only the synchronization operation ofFIG. 12E takes place. In that case, the flow of replacement fluid in theoperation of FIG. 12G is zero.

Note that to establish the effluent pump 574 speed, the controller maysimply calculate the shaft speed of a peristaltic pump equal to the sumof the shaft speeds corresponding to the command speeds used toestablish the dialysate and replacement fluid flow rates at the time ofthe respective synchronizations. Note that in all of the embodiments,the effluent pump may be increased above the synchronized rate toprovide a prescribed ultrafiltration rate as described herein andparticularly as described with reference to FIGS. 13A to 13C.

Note in a further variation of FIG. 12E, instead of synchronizing bytracking a pressure of the effluent pressure sensor 575.

Note that in this or any of the embodiments, including those defined bythe claims, the ratio of commanded pump speed to estimated flow may begiven by a pump curve that is based on inlet pressure, outlet-inletpressure difference, or a combination thereof, depending on suitabilityfor the type of pump used. Other factors may also be used for pump flowcompensation such as temperature and duration of use.

Referring to FIGS. 13A-13B, a summary of how synchronization is combinedwith pump inlet pressure compensation is described. Referring now toFIG. 13A Illustrated are two pumps 603 and 604 connected in series by aflow channel 605. The flow channel 605 may be a constant volume channelsuch as a bypass connection or a blood treatment device where one of thecompartments is sealed or it may be a “leaky” membrane channel such asin a blood treatment device where a pressure that establishes zerotransmembrane pressure condition will be established duringsynchronization. First, a controller generates a desired flow rate Q_(t)and converts that using a standard conversion 601 (e.g., formula, lookuptable) to a rotational frequency for each pump (ω1,i and ω2,respectively) where the first pump rotational frequency is an initialspeed for the desired flow rate Q_(t) which is updated duringsynchronization. Note that Qt and ω1,i and ω2 are ultimately commandedspeeds and a controller may bypass the conversion 601 and simply commandpump speed directly but typically inputs originate as desired flow ratesso the conversion between a physician's prescription in fluid volumeflow rate units would generally be converted into the same units in anapplication level control scheme until ultimately converted to arotational frequency (otherwise identified herein as pump speed). Thisis all merely to note that it will be understood in the discussion thatdiscussion of a commanded pump flow rate or pump speed relate to thesame thing. However it is recognized that the conversion 601 and 602 isnot exact which is why a synchronization is performed. The conversions601 and 602 may depend on the type of pump so different functionsf_(pt1) and f_(pt2) are shown but it should be understood that the pumpscould be of the same type in which case the functions would then be thesame.

Referring now to FIG. 13B, once flow is initially established betweenthe pumps 603 and 604, a synchronization procedure is performedaccording to any of the embodiments described above. As thesynchronization procedure progresses, the commanded flow rate (orequivalently, the pump speed or rotational frequency) of the pump 603 isvaried until sufficient data are obtained to estimate the commanded flowrate that matches the actual flow rate of the pump 604. As will beunderstood from the disclosure herein, the data the error variable andthe commanded pump speed of pump P correlated with the error variablewhere the error variable may be weight, volume (e.g., FIGS. 6A, 6B) orpressure (e.g., FIGS. 1A-1C including the treatment fluid-balancingalternative), pressure (e.g., FIGS. 3A-3E), or pressure drop (e.g., FIG.5 ). The commanded rate of the pump 603 is adjusted by a controller tofind a synchronized speed which is then recorded along with the inletpressure of the pump 604 that corresponds to it. Note that the pressure606 at the inlet of the second pump 604 may be known in advance if thezero-transmembrane flow condition is provided through pressuremanagement as in the example of FIGS. 3A-3E. Once the synchronized speedof the first pump 603 is established the pump 604 can be operatedthereafter at the commanded rate Qt and the upstream pump 603 at thesynchronized speed to achieve a flow balance as long as conditionsremain the same, for example, the pressure upstream of the pump 604remains the same.

Referring to FIG. 13C, after the synchronized speed of the pump 603 isestablished, the speed of pump 604 may thereafter be varied in responseto the inlet pressure 606 which has been identified above as “pressurecompensation.” Pressure compensation specifies a change of volume flowrate to the change inlet pressure of the pump 604. This ratio may varyover different pump speeds so multiple compensation curves may beprovided and used. Generally the compensation ratio or ratios areobtained by doing experiments with a specific pump and tubingconfiguration where peristaltic pumps are used.

Pressure compensation-based speed adjustment may be performedcontinuously or at predefined intervals during a treatment, for example.As noted above, the pressure 606 may change is if the treatment callsfor the pump 604 to be operated at a higher flow rate than pump 603 inorder to achieve a net flow out of the channel 605 (e.g., when thechannel 605 is a treatment device that can draw fluid from a patient'sblood through a membrane thereof), i.e., there is a net ultrafiltration.The speed of pump 604 can be lowered relative to the synchronized speedof pump 603 if a negative ultrafiltration rate is indicated by thecontroller or user.

To implement such predefined difference in the flows of the pumps, thespeed of pump 604 may be adjusted proportionately to the higher volumerate sought. For example, if the target flow rate Qt is 200 ml./min andthe ultrafiltration rate desired is 5 ml./min, then the pump 604 speedcan be commanded to 2.5% higher than Qt. The higher speed of the pump604 will result in a drop in pressure 606 which will produce a slightlylower rate of flow than the rate sought (2.5% higher than Qt). So thepump 604 speed must then be adjusted so that the rate of flow of pump604 according to the compensation ratio matches the incrementally higherrate sought. This may need to be done iteratively until the flow rate ofthe pump 604 converges to the estimated target value. This may be doneusing feedback control based on an optimization algorithm that minimizesthe error between the calculated Qt by varying the pump 604 rate.Alternatively, a function relating the rate of pressure drop to the flowdifference (the flow difference being equal to the ultrafiltration rate)may allow for the adjusted flow rate of the pump 604 to be predicted ina feedforward fashion.

The compensation ratio relates actual flow rate with a reference flowrate (in the example, Qt) by the following formula.Qact(t)=(1+α*(Pinlet(t)−Pref))*Q(t)

where Qact(t) is the actual flow rate through the compensated pump, a isa pump efficiency correction factor (i.e., the pump pressurecompensation coefficient), Pinlet(t) is the inlet pressure, and Pref isthe pressure where the pump was calibrated or synchronized (thereference point where the pump efficiency was measured). The pumppressure compensation coefficient α is dependent on the characteristicsof the pump and the pump tubing segment. In embodiments, the inletpressure correction may be 1.8%/25 mmHg deviation from the previous syncpressure. This value was obtained for a particular pump type and aparticular type of pumping tube segment after certain predefinedoperating conditions which include a break-in operating period and usinga certain fluid type. Thus the value is by no means limiting.

It should be clear from the foregoing how the correct value of a pumppressure compensation correction formula or lookup table may be obtainedfor other operating conditions. Note also that the above formula is aparticular relationship that can be expressed analytically quite simply.However, other types of pumps may have performance characteristics thatdepend on additional variables and on inlet pressure in other ways thatmake a different compensation function or lookup table desirable. Forexample, the flow may depend on other measurable variables such asinterval of time that the pumping tube segment has been in use (e.g.,number of roller strikes or shaft rotations of a peristaltic pumpactuator) and fluid temperature in addition to inlet pressure. Pumpoutlet pressure may also be included as a factor. In general correctionmay be handled by means of an offset proportional correction as inQact=[(1+α_(Pin)(Pin−Pref))(1+α_(life)(t))(1+α_(temp)(T−Tref))]Qref

where Qact is the compensated flow rate, Qref is the commanded flow rateas synchronized. Pref and Tref are the reference conditions of pressureand temperature and t is the amount of time or number of pump cycles forpump tube segment usage. Pin and Tare the current measure inlet pressureand fluid temperature, respectively.

It should be clear from the above, that the compensated flow rate maystill contain a systematic error relative to the actual flow rate andthat compensation merely adjusts for a departure from synchronized flowrates. Effectively this provides ratiometric proportioning with ratios(compensation factors) governing the offsets required to achieve adesired ultrafiltration from a patient.

During synchronization, the pressure of the channel between the pumpsundergoing synchronization may be unsteady and gradually, based onfeedback control using a PID control function implemented by acontroller, progress toward a synchronized state. There may be severalparameters for example, two time intervals defined for purposes ofcontrolling the synchronization procedure. A first time interval isdefined between the start of the synchronization procedure, when the twopumps are commanded to an initial speed, and the point at which thefeedback signal rate of change falls below a threshold. The latter maybe obtained by a moving average of the signal. The moving average may bedefined by an averaging window of a predefined shape and time width. Thesecond time interval may be an averaging period over which, after themoving average has fallen below the threshold, the pressure signal isaveraged. There is value in minimizing the lengths of these timeintervals. There may also be defined a threshold standard deviation forhigh frequency variations in the error signal that indicate “bad”synchronization. Together these criteria may establish when thesynchronization is completed and whether the data obtained from thesynchronization is valid.

Positive displacement pumps such as peristaltic pumps generate pressurepulses at their inlet and at their outlets. This causes the error signalused to synchronize pumps to be pulsatile. It has been discovered thatcombinations of certain speeds of the first and second pumps arrangedfor synchronization, particularly at low flow rates, generate pressurevariations that fail to converge in a short period of time producing“bad” or incomplete synchronizations according to reasonable timeperiods for the intervals discussed above. These undesirable speedcombinations can be discovered in the laboratory and used by thecontroller to allow the identification of allowed and non-allowedconditions of the pumps undergoing synchronization. To avoid non-allowedconditions while still providing a full range of flow rate combinations,the controller can use flow restrictions to generate artificially lowinlet pressures to one pump or the other in order to alter the pulsefrequency of that pump for a given flow rate. Thus, the controller maycontain a matrix correlating the first pump flow rate and the secondflow rate and for each, establish allowed ranges of inlet pressures forthe first pump that avoid the speed combinations that produce slow orbad synchronizations.

Referring now to FIG. 14A, a profile of instantaneous pressure signalfrom two synchronized pumps and a corresponding speed of the first pumpare shown. The data are merely representative and not limiting of thedisclosed embodiments. The variations 631 in the pressure signal aretypical, but a general trend is visible. FIG. 14B shows the same datawith a moving average calculated from the initial data indicated at 634.The remaining data are indicated at 632 and obtained from a model fittedto the moving average of data 634 to extrapolate a terminal averagevalue indicated at 630 which closely approximates the terminal averageobtained by averaging over a final period of the initial data 634. Thus,by fitting an exponential, gaussian, power series, or other function tothe data it may be possible to estimate the terminal average after theacquisition of a smaller amount of data over a shorter period of time.The amount of data and the probability of error may vary depending onthe conditions, for example, at low flow rates, a longer interval ofdata may be required. The best parameters to use will be best obtainedthrough laboratory experiments with the specific pump types, materials,and operating conditions for the treatment being performed.

It will be observed that the foregoing shows an example of a way todynamically determine a synchronized speed of the upstream pump withoutcoming to a full synchronization equilibrium. Thus the embodimentillustrates one example of a method for controlling flow in a fluidcircuit, the method being applicable to any blood treatment system thatregulates the net ultrafiltration of a patient by balancing fluidwithdrawn from a blood treatment device against fluid pumped into theblood treatment device by controlling the relative volume displacedduring a treatment by independently-regulated inflow and outflowvolumetric pumps. In the method, during a testing mode, the controllerconnects the inflow and outflow pumps directly while measuring a changein a flow property. The flow property may be flow rate, pressure, ormass. Next, the controller stores synchronized flow data representingthe change measured by said measuring and then calculates, from thesynchronized flow data, control parameters for regulating the inflow andoutflow volumetric pumps. The method continues with performing atreatment including controlling a net flow of fluid to or from a patientby controlling said inflow and outflow volumetric pumps responsively tosaid control parameters. During the testing mode, the inflow and outflowpumps are not adjusted to be synchronized fully. In particularembodiments the operation of connecting the inflow and outflow pumpsdirectly includes connecting the inflow and outflow pumps through ablood treatment device. In additional embodiments, the operation ofconnecting the inflow and outflow pumps directly includes defining afixed-volume flow channel between the inflow and outflow pumps. The flowproperty may include pressure. The method may further include, duringthe testing mode, calculating a moving average of the flow property andfitting the same to a curve, wherein the calculating includes fittingthe curve to a resulting fitted curve. The method may further includecalculating, during the testing mode, a moving average of the flowproperty and fitting the same to a curve, wherein the calculatingincludes extrapolating the fitted curve to a corresponding point inpump-speed-to-time curve where the curve is calculated to be flat.

The above methods may be implemented by a controller of a treatmentmachine. For example, a system for controlling flow in a fluid circuitmay have a blood treatment system with a reconfigurable fluid circuitand blood treatment device (for example a disposable fluid circuit andactuators controlled by the machine to define multiple flow pathsthrough the fluid circuit). The system may have inflow and outflowvolumetric pumps that are controlled by the controller to regulate thenet ultrafiltration of a patient by balancing fluid withdrawn from ablood treatment device against fluid pumped into the blood treatmentdevice by controlling the relative volume displaced during a treatmentby independently regulating the speeds of the inflow and outflowvolumetric pumps. The controller may receive signals from the flow asensor indicating the flow property.

Referring now to FIG. 15A, an additional mechanism is described forproviding a zero transmembrane flow condition to allow the measurementof treatment device pressure at this condition. The circuit 675 of FIG.15A may correspond to that of FIG. 11 or a subset thereof with anadditional set of components. The added components include thefollowing. A multi-chamber element 641 has a rigid housing and aflexible diaphragm dividing the internal volume of the multi-chamberelement 641 such that as one side of the diaphragm receives a fluid atone end of the multi-chamber element 641, the other side's volume isdiminished by precisely the same amount forcing an equal volume of fluidout the other end. Thus, as a pump 643 forces fluid into themulti-chamber element 641, fluid from the other end is pushed out at thesame rate as pumped in. Pinch clamps 647 and 646 as well as pinch clamps645 and 642 serve to allow the controller to selectively isolate themulti-chamber element 641 and the treatment device 114 as will beobserved from the following description.

FIG. 15B shows the circuit 675 in a configuration for filling a freshtreatment fluid side of the multi-chamber element 641. Blood is pumpedby a blood pump 563 as indicated. The fresh treatment fluid pump 573 andpump 643 are operated with clamps 650, 642, 645, and 581 in openpositions to flow treatment fluid into one side of the multi-chamberelement 641 while emptying the other side into the waste line. The pump643 is operated in a reverse direction as indicated by the direction ofarrowhead in the pump symbol. Effluent pump 574 may be operated toconvey waste fluid to the drain (or waste collector) 126. This operationcharges the multi-chamber element 641 with fresh treatment fluid fromthe treatment fluid source 124. FIG. 15C shows a closed loop beingformed by operation of the indicated clamps with the pump 643 operatedin the forward direction. The volume of the closed loop flow path iscompletely fixed as can be confirmed by inspection and the descriptionof multi-chamber element 641. Thus, even as there is a flow in thenon-blood compartment through the treatment device 114, thetransmembrane flow is zero. The valve 581 is opened to allow thepressure in the closed loop to communicate with the effluent pressuresensor 575. Thus, the pressure of the non-blood compartment of thetreatment device 114 may be measured under zero transmembrane flowconditions while fresh treatment fluid is circulated through thetreatment device, thereby continuing dialytic cleansing of the bloodduring this initial step of pump synchronization. The remaining stepsmay completed as indicated and discussed relative to FIGS. 12D to 12Fand other embodiments.

Note that in FIGS. 15A-15C, the double lines indicate flow paths in aflow is established and the single lines indicate a flow path in whichno flow is present. Clamps are illustrated as in FIGS. 12A to 12F.

It should be evident from the discussion of FIGS. 12A through 12F andelsewhere that the disclosed subject matter provides a method and asystem for controlling fluid flow in a fluid circuit, in embodiments, afluid circuit that includes treatment fluid and blood portions. Themethod may include connecting first inflow and outflow lines to one ofblood and non-blood compartments of a blood treatment device andconnecting second inflow and outflow lines to the other of blood andnon-blood compartments of the blood treatment device. Then using acontroller, regulating a speed of a first inflow pump connected to thefirst inflow line to establish a flow into said one of blood andnon-blood compartments of a blood treatment device. The method includesregulating a speed of a first outflow pump connected to the firstoutflow line to establish a flow out of said one of blood and non-bloodcompartments of a blood treatment device and detecting a pressure of atleast one of the blood and non-blood compartments, said pressureindicating a magnitude of a difference between the rates of the flowsinto and out of said one of blood and non-blood compartments. The methodincludes calculating a flow control parameter responsively to saidpressure and thereafter regulating a net transfer of fluid between theblood and non-blood compartments responsively to the control parameter.In variations, the method includes during the detecting, flowing fluidthrough the second inflow and outflow lines. In further variations, themethod may include, during said detecting, blocking the flow of fluidthrough the second inflow and outflow lines such that the first inflowand outflow lines and said one of blood and non-blood compartments of ablood treatment device constitute a fixed volume fluid channel. Thepressure may indicate a magnitude of a transmembrane transport betweenthe blood and non-blood compartments. This can be due to the fluidchannel being a fixed volume channel or due to the regulation of a pumpspeed such that a zero-transmembrane flow is established. The pressureat which zero-transmembrane flow is established may be determinedautomatically by the controller using the methods and mechanismsdescribed herein. The pressure may indicate a magnitude of atransmembrane transport between the blood and non-blood compartments andthe calculating includes comparing the pressure to a predefinedthreshold pressure indicative of zero magnitude of a transmembranetransport between the blood and non-blood compartments.

Thus, it will be observed, that the synchronization method allows thepumps to be synchronized during a treatment mode (albeit, inembodiments, a briefly-interrupted treatment mode) or during a primingstage. It may also be done at other times such as a factory calibration.Advantageously, the synchronization may be done without removing bloodfrom the blood compartment of the treatment device. Further,advantageously, the method may be applied to synchronize inflow andoutflow pumps on the blood side or the treatment fluid side of thetreatment device. That is, in the embodiment delineated immediatelyabove, the first inflow and outflow lines may be blood lines ortreatment fluid lines. Instead of pressure, one may substitute volumeflow measurement technique described in connection with FIGS. 6A and 6Bor the flow measurement device described with reference to FIG. 5 . Itshould be clear that the pressure signal from which the flow controlparameter is calculated may arise due to the blockage of any shift offluid between the blood and non-blood compartments (e.g., flow through amembrane separating the compartments) or simply the resistance of themembrane. The pressure or the rate of change of pressure may indicatesynchronization. In either case, the inflow and outflow pumps may beregulated such that the outflow pump's inlet pressure is at a desiredoperating pressure determined to be present during a treatment.

The pressure may indicate a magnitude of a transmembrane transportbetween the blood and non-blood compartments and the calculating mayinclude comparing the pressure to a predefined threshold pressureindicative of zero magnitude of a transmembrane transport between theblood and non-blood compartments. In this case, the method may includedetermining the predefined threshold pressure by detecting a pressure ofthe at least one of the blood and non-blood compartments while blockingtransport between the blood and non-blood compartments.

The pressure may indicate indicate a magnitude of a transmembranetransport between the blood and non-blood compartments, the calculatingmay includes comparing the pressure to a predefined threshold pressureindicative of zero magnitude of a transmembrane transport between theblood and non-blood compartments and the method may further includedetermining the predefined threshold pressure by detecting a pressure ofthe at least one of the blood and non-blood compartments while blockingtransport between the blood and non-blood compartments and whileestablishing flow through the second inflow and outflow lines at apredefined flow rate.

Referring to FIG. 16 , in any of the embodiments involvingsynchronization of two pumps, an error may be generated by a gradualchange in the ratio of actual flowrate to commanded flowrate. Thus, attime to, during or before a treatment, a synchronization may beperformed S300 in which the commanded rate of an upstream pump, Pump 1,that generates a flow equal to the commanded flow rate for thedownstream pump, Pump 2. At a later time, during treatment, thesynchronized rate may be updated S301 resulting a new commanded flowrate for Pump 1. At S302, the difference between the new and oldcommanded flow rates yields a flow rate difference, calculated at S302,which may may arise progressively during the time from the firstsynchronization to the later one. The flow rate difference may beinterpolated between synchronizations and integrated over the assumeddistribution of the change in the synchronized commanded rate over time.Assuming the difference accrued linearly over the time between the firstsynch and the second, a surfeit or deficiency may be calculated from thetriangle function, i.e., multiplying the time between synchronizationsby ½ the difference between the old and new Pump 1-synched commandedflow rates. If the later synchronized speed is higher, then this amountmay be added to the ultrafiltration budget so that the required volumeto be ultrafiltered during a remainder of the treatment will beincreased. If the later synchronized speed is lower, then this amountmay be subtracted from the ultrafiltration budget. S306. At S308, a newultrafiltration rate may be calculated so that by the time the treatmentis completed, the entire budget has been spent. Thereafter the budgetmay be applied to perform a remainder of the treatment S310 or theprocess may be repeated if additional synchronizations are to beperformed. The parameters are illustrated graphically in FIG. 17A whichshows two bar graphs for the two command rates for the first pump aftersynchronization with an exaggerated change. The shaded trianglesuperimposed on the bars indicates the cumulative UF shortfall when thenew command rate of the first pump shows that a higher rate is requiredto keep up with the second pump. The symbol Q represents the commandedpump rate.

Note that if, in a procedure similar to FIG. 16 , is performed, in whicha subsequent synchronization is performed at a different Pump 2commanded flow rate than the first synchronization, a budget surfeit ordeficiency can still be calculated if the difference between the oldPump 2 commanded flow rate is removed from the calculation. Thus,subtracting Pump 2-commanded new from Pump 2-commanded old and thensubtracting this difference from the old and new Pump1-commanded-synched rates gives a Pump 1-commanded-synched that can beused to be used for the interpolation calculation. The parameters areillustrated in FIG. 17B. The new synchronized command rate for the firstpump is reduced by the difference between the new and old second pumpcommand rates and the ultrafiltration shortfall calculated from thereduced rate as before.

FIGS. 18A-18B illustrate the generation and use of a map of commandedflow and pressure conditions for determining the synchronized commandspeed of a slave pump 702 responsively to a command speed of a masterpump 704 according to various embodiments of the disclosed subjectmatter. For example, the method may be used to obtain a formula orlookup table to calculated the rates of a replacement fluid pumped byFP2 (FIG. 11 ) for a given EP and target effluent pump speed (FP3). FIG.18A shows a generic synchronization scheme with symbols used in FIG. 18Bwith a first pump 708 (FP2 refers to FIG. 11 dialysate pump as anexample) and a second pump 710 (FP3 refers to FIG. 11 waste—oreffluent—pump as an example). The two pumps 708 and 710 are linked by aflow channel 714 which may be any of any type including those of thevariety of embodiments disclosed herein. The flow balance sensor 706indicates a flow mismatch between the two pumps 708 and 710. EPindicates the waste line pressure (or effluent pressure) indicated inFIG. 11 , for example.

Referring to FIG. 18B at S400, master pump FP3 is run at a commandedrate of F2 and slave pump FP2 is synchronized with it at a predefinedpressure of the effluent pump EP, for example, 100 mmHg. Thesynchronized speed of FP2 and the measured value of EP are recorded. AtS402, master pump FP3 is run at a commanded rate of F2 and slave pumpFP2 is synchronized with it at a predefined pressure of the effluentpump EP, for example, 300 mmHg. The synchronized speed of FP2 and themeasured value of EP are recorded. At S404, master pump FP3 is run at acommanded rate of F3 and slave pump FP2 is synchronized with it at apredefined pressure of the effluent pump EP, for example, 100 mmHg. Thesynchronized speed of FP2 and the measured value of EP are recorded. AtS406, master pump FP3 is run at a commanded rate of F3 and slave pumpFP2 is synchronized with it at a predefined pressure of the effluentpump EP, for example, 300 mmHg. The synchronized speed of FP2 and themeasured value of EP are recorded. At S410, the recorded speeds andpressure values are fitted to a function to allow the calculation of thesynchronized command slave pump rate responsively to the commandedmaster pump rate and pressure. At S414, the master pump is adjustedaccording to the pressure compensation coefficient and the differencebetween the desired EP and the measured magnitude.

At S412, the function is used to calculate a synchronized rate for theslave pump FP2 responsively to a commanded master pump rate and acurrent effluent pressure EP. The EP pressure used for obtaining thesynchronized rates at steps S400-S406 are predefined values. The targetindependent variable used in S412 is the measured value of the effluentpressure when the blood is flowing through the hemofilter and there isno flow from the effluent pump. At S414, during a hemofiltrationtreatment, the replacement fluid pump RF2 may be set using the formulaor lookup table and a current measured EP. With pressure compensationrunning, as the effluent pressure departs from the EP originally enteredin the formula, the speed of the effluent pump is adjusted accordingly.

In any of the disclosed embodiments, the pressure used forsynchronization, which corresponds to a condition of zero flow throughthe membrane of the treatment device, may be an average of the treatmentfluid inlet and outlet pressures, the treatment fluid outlet pressurealone, the pressure of the non-blood compartment of a speciallyconstructed blood treatment device that permits the pressure inside thetreatment device to be measured with a single pressure transducer, anaverage of the blood inlet and outlet pressures, the blood outletpressure alone, or the pressure of the blood compartment of a speciallyconstructed blood treatment device that permits the pressure inside thetreatment device to be measured with a single pressure transducer.

In all of the embodiments, pinch clamps can be replaced with other typesof valves and circuit elements, for example, stopcocks, flow switchers,etc.

In any of the disclosed embodiments, the oncotic pressure of blood maybe measured by halting a flow of treatment fluid and measuring thepressure difference between the blood and treatment fluid sides of thetreatment device. This may be done each time the pumps are synchronizedor it may be done independently for the purpose of sampling the bloodoncotic pressure. The samples of oncotic pressure may be used tocalculate a trend that may be compared to a predefined trend in oncoticpressure. The comparison may indicate that the pace of fluid withdrawalis drawing down the fluid in the blood compartment too fast relative tothe patient's ability to replenish it from the upstream fluidcompartments such as the interstitial and cellular compartments. Therestoration of fluid to the blood compartment is known in the art asfluid rebound. Too high rate of ultrafiltration can cause a temporaryhypovolemia which can be detrimental.

The controller may store a predefined rate of change in oncotic pressurethat is permitted and slow the rate of ultrafiltration to fall under, orat that rate. The controller may compare the oncotic pressure to apredefined value and control a duration of the treatment so that theoncotic pressure is permitted to reach that value. Note that instead ofstoring actual values of oncotic pressure, data responsive to it may bestored, such as a derivative of oncotic pressure and or combinationswith other variables. For example, oncotic pressure may be combined witha hematocrit sensor signal to produce a combined parameter indicatingthe patient's fluid load. In further embodiments, the controller mayhalt, or otherwise vary, the rate of ultrafiltration and combine dataindicative of the varying rate of ultrafiltration with the oncoticpressure trend data in order to determine the fluid load or the rate offluid rebound. A combined parameter such as a ratio of rate of oncoticpressure change to rate of ultrafiltration may be calculated and used tocontrol the rate of ultrafiltration or the duration of ultrafiltration(or duration of treatment). The rate of ultrafiltration may be variedcontinuously during a treatment cycle responsively to the trend. Therate may be varied so as to decline progressively during a treatmentaccording to predefined constraints on the oncotic pressure or rates ofchange thereof. As indicated, the oncotic pressure may indicate when thepatient has reached a dry weight by measuring the magnitude of oncoticpressure relative to a predefined value (which may be custom for thepatient) or the rate of fluid rebound, or the magnitude of the change inoncotic pressure over a test interval during which a predefined rate ofultrafiltration (for example zero rate of ultrafiltration) ismaintained.

In all of the embodiments, pinch clamps can be replaced with other typesof valves and circuit elements, for example, stopcocks, flow switchers,etc.

In any of the embodiments, a newly connected fluid circuit, connected toa treatment machine having sensors and actuators to engage it, may besubjected to a break-in interval during priming to condition the pumpingtube segments before synchronization is performed, or at least reliedupon for fluid balance. In an embodiment, in a treatment machine thatcontrols the total volume of fluid flowing into or from a patientagainst the total volume of fluid drawn from the patient by regulatingthe relative speeds of peristaltic pumps that flow fluid in a fluidcircuit connected to the patient, a special priming mode is implemented.In the priming mode, fluid is pumped through the fluid circuit to primeat least the treatment fluid portion of the attached fluid circuit. Apredefined break-in period sufficient to subject the inflow and outflowtreatment fluid pumps—the pumps relied upon for fluid balance andultrafiltration—are subjected to a predefined number of roller strikesprior to performing a synchronization. The break-in interval, inembodiments, may last for greater than five minutes, before establishinga synchronization mode or a treatment in which the peristaltic pumps arerelied upon to control a net flow of fluid into or from the patient. Inembodiments, the treatment machine is a hemodialysis machine or ahemofiltration machine where the pumps regulate the flow of dialysateinto and out of a dialyzer or hemofilter.

Note that as used herein, embodiments refer to the embodiments describedin the specification as well as any independent claim and anycombination of an independent claim with any combination orsub-combination of the claims depending from an independent claim.

In the foregoing embodiments, the fresh treatment fluid pump pumpingrate was determined by the controller, during treatment, from afunction, or equivalent, that depended on the rate of the wastetreatment fluid pump and the blood compartment pressure (Ave Pb). Inalternative embodiments, the fresh treatment fluid pump may be feedbackcontrolled on a balanced pressure signal calculated as the differencebetween the non-blood compartment pressure, Ave Ptf, and Ave Pb offsetby the error and oncotic pressure which are both stored by thecontroller. Then the determined fresh treatment fluid pumping rate canbe changed to obtain the prescribed ultrafiltration rate. In themodified method, S72 is replaced by an operation in which the freshtreatment fluid pump is negative feedback controlled by the calculatederror signal. This may be employed, for example instead of thefeedforward technique of S72.

In the foregoing embodiments, the TMP is provided as a function of AvePb and Qtfw, however, the TMP error may not be a function of theseindependent variables in which case it may be stored as a fixed value inthe controller.

Note that as the term is used herein, “balanced” flow may refer to equalflows or flows that differ by a predefined amount, for example toaccount for ultrafiltration. During synchronizations, balanced flows mayhave a zero differential, however, an arbitrary predefined offset fromequal flows may still be accommodated using the techniques ofsynchronization, as should be clear to the skilled practitioner. As termis used herein, balanced may refer to flows that are balanced but offsetby a predefined ultrafiltration rate.

In any of the embodiments, the fluid in the treatment fluid circuit andtreatment device non-blood compartment may be a priming fluid as is usedcommonly during priming stage in preparation for a treatment.

In any of the embodiments, the ultrafiltrate or net transfer of fluidfrom a patient can be positive or negative. A negative ultrafiltraterefers to a net transfer of fluid to a patient while a positiveultrafiltrate refers to a net transfer from a patient. The term balancedin reference to flow may refer to zero net ultrafiltrate volume or rateor a target net ultrafiltrate volume or rate. It does not necessarilymean equal flows in and out of a priming fluid source/sink or patient.

In other embodiments, the oncotic pressure of blood may be measured asdescribed above and used for real-time feedback control of thedifference in the average pressure in the blood compartment minus thepressure in the treatment fluid compartment (the compartments beingcompartments of the blood treatment device) minus the oncotic pressure.The real time feedback control on the pressure difference may continueduring a treatment to control the relative speeds of the treatment fluidpumps in a configuration such as that of FIG. 3A and FIG. 7 . Theoncotic pressure may be measured again at certain points duringtreatment and used to provide the other functions discussed above.

According to first embodiments, the disclosed subject matter includes anapparatus for controlling flow in a fluid circuit with a controllerconnected to a data store that stores parameters and procedural data. Atreatment machine with arterial and venous blood pump actuators isconnected to be controlled by the controller. The treatment machine hasa medicament pump actuator and a valve actuator connected to becontrolled by the controller. The treatment machine has at least onepressure sensor. The treatment machine has a receiving adapter shaped toreceive a blood circuit has arterial and venous lines joined by atreatment device such that the arterial and venous pump actuatorscontrol flow to and from the treatment device and to permit the at leastone pressure sensor to indicate pressure in the blood circuit,respectively. The treatment machine receiving adapter is further shapedto receive a medicament circuit has fresh and waste lines joined by thesame treatment device such that medicament pump is able to pumpmedicament through one of the fresh and waste lines and the valveactuator is able to prevent flow in the other of the fresh and wastelines. The treatment component is of a type that permits a transfer offluid between the predefined type of blood circuit and the predefinedtype of medicament circuit. The procedural data defines a method ofregulating a ratio of arterial and venous blood flow rates bycontrolling speeds of the arterial and blood pump actuators over atreatment interval in order to generate a net fluid transfer in anattached instance of said blood circuit responsively to an ultrafiltrateparameter and a compensation parameter stored in the data store. Theultrafiltrate parameter indicates said net fluid transfer. Theprocedural data further defines a method of calculating the compensationparameter according to which the controller controls the medicament pumpand the valve actuator to block flow into and out of the treatmentdevice and controls the arterial and venous pump actuators to achieve anequal flow through the treatment device through error controlresponsively to the pressure indicated by the at least one pressuresensor. The calculating is responsive to a ratio of commanded speeds ofsaid arterial and venous pump actuators.

Variations of the first embodiments include further first embodiments inwhich the treatment device is a dialyzer. Variations of the firstembodiments include further first embodiments in which the treatmentdevice separates the blood and medicament circuits by a membrane.Variations of the first embodiments include further first embodiments inwhich the ultrafiltrate parameter indicates a net ultrafiltrate volumefor a single treatment cycle. Variations of the first embodimentsinclude further first embodiments in which the valve actuator is a pinchclamp that is operated by a linear actuator. Variations of the firstembodiments include further first embodiments in which the pinch clampengages a tube portion of said medicament circuit. Variations of thefirst embodiments include further first embodiments that include areplacement fluid pump actuator, connected to be controlled by thecontroller, that is positioned such that the receiving adapter engages areplacement fluid line that connects a source of replacement fluid tosaid blood circuit for predilution or postdilution of blood. Variationsof the first embodiments include further first embodiments in whichaccording to the method defined by said procedural data, the controllercontrols the replacement fluid pump actuator to block flow into and outof the blood circuit, except by way of the arterial and venous lines,when said controller controls the arterial and venous pump actuators toachieve an equal flow through the treatment device. Variations of thefirst embodiments include further first embodiments that include a drugpump actuator, connected to be controlled by the controller, that ispositioned such that the receiving adapter engages a replacement fluidline that connects a source of a drug to said blood circuit injectioninto blood flowing in said blood circuit. Variations of the firstembodiments include further first embodiments in which according to themethod defined by said procedural data, the controller controls the drugpump actuator to block flow into and out of the blood circuit, except byway of the arterial and venous lines, when said controller controls thearterial and venous pump actuators to achieve an equal flow through thetreatment device.

According to second embodiments, the disclosed subject matter includesan apparatus for controlling flow in a fluid circuit. The apparatus hasa treatment machine with pumping actuators, sensors, at least one flowregulator. The treatment machine has a controller connected to controlthe pumping actuators and at least one flow regulator, receive signalsfrom the sensors in order to implement a therapeutic treatment in atreatment mode and perform a synchronization in a synchronization mode.The treatment machine is adapted to receive a predefined fluid circuithas a plurality of fluid lines includes first and second fluid lines andother fluid lines all interconnected by the fluid circuit, each of thefluid lines is used to transport a fluid during the treatment mode. Theat least one flow regulator is arranged to selectively block flow in arespective one of said fluid lines. The plurality of pump actuators eachis arranged to selectively pump fluid or block flow in a respective oneof said fluid lines, first and second of the pump actuators is engagedwith the first and second fluid lines. The controller is programmed to,during the synchronization mode:

-   -   command first and second pump actuators of the plurality of pump        actuators to flow fluid between the first and second fluid        lines;    -   block flow in the plurality of fluid lines other than the first        and second fluid lines to define a fixed volume flow channel        between the first and second fluid lines; and    -   regulate the relative speeds of the first and second pump        actuators responsively to a pressure sensor of the sensors to        estimate relative rates of said first and second pump actuators        that achieve a constant pressure in the fixed volume flow        channel.

The controller is further programmed to calculate a control parameterresponsive to said relative rates, and, during the treatment mode,regulate a net flow through the other fluid lines by commanding therelative rates of said pump actuators responsively to said controlparameter.

Variations of the second embodiments include further second embodimentsin which some of the fluid lines are interconnected by a treatmentdevice. Variations of the second embodiments include further secondembodiments in which the first and second fluid lines are interconnectedby a treatment device. Variations of the second embodiments includefurther second embodiments in which the treatment device is a dialyzer.Variations of the second embodiments include further second embodimentsin which at least one of the fluid lines is connected to a containerstoring a drug. Variations of the second embodiments include furthersecond embodiments in which at least one of the fluid lines is connectedto a container storing a replacement fluid. Variations of the secondembodiments include further second embodiments in which the treatmentdevice is a dialyzer, said first fluid line is a fresh dialysate lineand said second fluid line is a waste dialysate fluid line. Variationsof the second embodiments include further second embodiments in whichthe first and second fluid lines are interconnected by a treatmentdevice and at least two of the other fluid lines are blood linesconnected to the treatment device, the blood lines are interconnected tothe first and second fluid lines through a membrane. Variations of thesecond embodiments include further second embodiments in which the bloodlines are engaged by respective pump actuators.

Variations of the second embodiments include further second embodimentsin which the first and second fluid lines are engaged by a pump actuatorand a valve actuator, respectively. Variations of the second embodimentsinclude further second embodiments in which the first and second fluidlines are blood lines interconnected by a treatment device and at leasttwo of the other fluid lines are medicament lines connected to thetreatment device, the blood lines are interconnected to the medicamentlines through a membrane. Variations of the second embodiments includefurther second embodiments in which the medicament lines are engaged byrespective pump actuators. Variations of the second embodiments includefurther second embodiments in which the medicament lines are engaged bya pump actuator and a valve actuator, respectively. Variations of thesecond embodiments include further second embodiments in which the firstand second fluid lines and at least one of the other fluid lines areinterconnected by a treatment device. Variations of the secondembodiments include further second embodiments in which the first andsecond fluid lines and at least two of the other fluid lines areinterconnected by a treatment device. Variations of the secondembodiments include further second embodiments in which the first andsecond fluid lines and at least two of the other fluid lines areinterconnected by a treatment device, the at least two is connected totransport fresh medicament and waste medicament. Variations of thesecond embodiments include further second embodiments in which thecontrol parameter defines an adjustment of the commanded relative ratesof the first and second pump actuators. Variations of the secondembodiments include further second embodiments in which the other fluidlines include at least one replacement fluid line connected to a bloodline. Variations of the second embodiments include further secondembodiments in which the other fluid lines include at least one drugfluid line connected to a blood line. Variations of the secondembodiments include further second embodiments in which the first andsecond fluid lines form a continuous flow path of either blood from apatient that is returned to a patient or medicament that is supplied toa treatment device and drawn from a treatment device. Variations of thesecond embodiments include further second embodiments in which none ofthe first, second, or other fluid lines is used exclusively during thesynchronization mode for flowing fluid therethrough. Variations of thesecond embodiments include further second embodiments in which all ofthe first, second, or other fluid lines carry at least one of blood,medicament, or a drug during the treatment mode, whereby no additionalfluid lines are required for the synchronization mode.

According to third embodiments, the disclosed subject matter includes ablood treatment machine that has a controller connected to control freshand waste treatment fluid pumps connected to flow treatment fluid to andfrom a blood treatment device has blood and treatment fluidcompartments, respectively, a blood pump connected to flow fluid throughthe blood treatment device blood compartment, and inlet and outletpressure sensors indicating pressures into and out of the treatmentdevice blood compartment. The controller is programmed to implement amethod. The method includes storing operating conditions in a datastore, the operating conditions includes combinations of target averageblood pressures in the treatment device and target flow rates of thetreatment fluid pumps. The method further includes an outer control loopaccording to which, for each of the average blood pressures, thecontroller commands the blood pump, with the treatment fluid pumps off,to circulate priming fluid through the treatment device bloodcompartment at a respective target average blood pressure and records ameasured actual average blood compartment pressure in the treatmentdevice, the average is indicated by the inlet and outlet pressuresensors. According to an inner control loop, which may be embedded inthe outer control loop, for each of the treatment fluid pump target flowrates that corresponds to a current target blood pressure in the storedoperating conditions, the controller commands the treatment fluid pumpsto circulate fluid through the treatment device treatment fluidcompartment at a respective target treatment fluid flow rate andcontrolling the absolute and relative rates of fresh and waste treatmentfluid pumps to achieve an equilibrium condition of equalized flow and anaverage pressure indicated by the inlet and outlet pressure sensorsequal to said recorded measured actual average blood pressure andrecords synchronization data includes commanded rates of the treatmentfluid pumps and indications by the inlet and outlet pressure sensorscorresponding to the equilibrium condition. The method includes fittinga function, or an equivalent of a function (hereafter, operator), to thesynchronization data that relates a slave rate of one of the commandedfresh and waste treatment fluid pumps to a combination of a master rateof the other of the commanded fresh and waste treatment fluid pumps andan average of the recorded indications of the inlet and outlet pressuresensors.

Variations of the third embodiments include further third embodiments inwhich the method further includes controlling a patient's fluid balanceresponsively to the operator. Variations of the third embodimentsinclude further third embodiments in which the controlling to patient'sfluid balance includes controlling a ratio of speeds of said fresh andwaste treatment fluid pumps responsively to said operator. Variations ofthe third embodiments include further third embodiments in which thedimensions of said one of the commanded fresh and waste treatment fluidpump rate are revolutions per unit time. Variations of the thirdembodiments include further third embodiments in which the controlling apatient's fluid balance includes reading a fresh and waste treatmentfluid pump rate or flow rate from a prescription, generating a commandto said fresh and waste treatment fluid pumps responsive to said readrate, and controlling a ratio of speeds of said fresh and wastetreatment fluid pumps responsively to said operator. Variations of thethird embodiments include further third embodiments in which thecontrolling a patient's fluid balance includes reading a fresh and wastetreatment fluid pump rate or flow rate from a prescription, generating acommand to operate the other of the commanded fresh and waste treatmentfluid pumps at a current commanded speed indicated by said read rate andapplying the current commanded speed to said operator, calculating acurrent measured average blood compartment pressure indicated by theinlet and outlet pressure sensors and applying said current measuredaverage to said operator, and controlling one of said fresh and wastetreatment fluid pumps responsively to an output of said operator.Variations of the third embodiments include further third embodiments inwhich the controlling a patient's fluid balance further includesfeedback-controlling the speed of the one of the commanded fresh andwaste treatment fluid pumps until a newly calculated average bloodcompartment pressure indicated by the inlet and outlet pressure sensorsis equal to the previously calculated current measured average bloodcompartment pressure. Variations of the third embodiments includefurther third embodiments in which the controlling a patient's fluidbalance further includes reading ultrafiltration data responsive to anultrafiltrate volume and changing a ratio of speeds of the fresh andwaste treatment fluid pumps responsively to said ultrafiltration data.

According to fourth embodiments, the disclosed subject matter includes,an apparatus for controlling flow in a fluid circuit. A treatmentmachine has flow regulators and sensors, the flow regulators includespumping actuators. The treatment machine has a controller connected tocontrol the flow regulators and receive signals from the sensors toimplement a therapeutic treatment by regulates the flow of blood andtreatment fluid when a predefined fluid circuit is connected inoperative engagement with the flow regulators and sensors. Thepredefined fluid circuit has a plurality of fluid lines includes firstand second fluid lines and other fluid lines all interconnected by thefluid circuit, each of the fluid lines are used to transport a fluidduring the treatment mode in order to implement the therapeutictreatment. The flow regulators are controlled by the controller, duringa synchronization mode thereof, to selectively block flow in first onesof the fluid lines while selectively pumping fluid serially throughsecond ones of the fluid lines such that first and second pumpingactuators pump fluid in a fixed volume channel that interconnects thesecond ones of the fluid lines, the fixed volume channel are sealed inpart by the first ones of the fluid lines. The controller, during thesynchronization mode, regulates the relative speeds of the first andsecond pumping actuators responsively to at least one of the sensors toestimate commanded rates of the first and second pumping actuatorscorresponding to equal flows throughout the fixed volume channel andderiving one or more control parameters permitting the controller toimplement a predefined ratio of flow rates by the first and secondpumping actuators during a treatment mode of the controller. The flowregulators are controlled by the controller to, during the treatmentmode, regulate a net flow through the second ones of the fluid lines bycommanding the relative rates of the first pump actuator responsively tothe one or more control parameters.

In additional embodiments thereof, the fourth embodiments include onesin which some of the first and second fluid lines are interconnected bya treatment device. In additional embodiments thereof, the fourthembodiments include ones in which the first fluid lines are blood linesand the first and second pumping actuators are arterial and venous bloodpumping actuators. In additional embodiments thereof, the fourthembodiments include ones in which the treatment device is a dialyzer. Inadditional embodiments thereof, the fourth embodiments include ones inwhich at least one of the fluid lines is connected to a containerstoring a drug. In additional embodiments thereof, the fourthembodiments include ones in which at least one of the fluid lines isconnected to a container storing a replacement fluid. In additionalembodiments thereof, the fourth embodiments include ones in which thetreatment device is a dialyzer and the second fluid lines are freshdialysate line waste dialysate fluid lines, respectively. In additionalembodiments thereof, the fourth embodiments include ones in which thefirst and second fluid lines are interconnected by a treatment device,the second fluid lines are blood lines and the first and second pumpingactuators are fresh and waste treatment fluid blood pumping actuators.In additional embodiments thereof, the fourth embodiments include onesin which the first fluid lines are separated from the second fluid linesby a membrane of the treatment device. In additional embodimentsthereof, the fourth embodiments include ones in which during thesynchronization mode, the first and second pumping actuators areoperated at multiple speeds to generate multiple one or more controlparameters by regulates the relative speeds of the first and secondpumping actuators to achieve equal flows of multiple magnitudes. Inadditional embodiments thereof, the fourth embodiments include ones inwhich the sensors include pressure sensors. In additional embodimentsthereof, the fourth embodiments include ones in which pressure datacorresponding to signals from the pressure sensors are recorded duringthe synchronization mode and included in the at least one controlparameter, the pressure signals are used by the controller to generate acommanded speed of at least one of the first and second pumpingactuators to account for differences between the pressure data andpressure signals during the synchronization mode and the treatment mode.In additional embodiments thereof, the fourth embodiments include onesin which the sensors include a weight sensor, the controller determiningequal flows in the second fluid lines from the weight sensor. Inadditional embodiments thereof, the fourth embodiments include ones inwhich the controller determines equal flows in the second fluid linesfrom a state where weight indicated by the weight sensor is unchanging.In additional embodiments thereof, the fourth embodiments include onesin which the sensors include a pressure sensor, the controllerdetermining equal flows in the second fluid lines from the pressuresensor. In additional embodiments thereof, the fourth embodimentsinclude ones in which the controller determines equal flows in thesecond fluid lines from a state where pressure indicated by the weightsensor is unchanging. In additional embodiments thereof, the fourthembodiments include ones in which the flow regulators include at leastone control valve that engages with one of the first fluid lines. Inadditional embodiments thereof, the fourth embodiments include ones inwhich the flow regulators include a third pumping actuator that engageswith one of the first fluid lines, the third pumping actuator are haltedduring the synchronization mode to prevent flow in the one of the firstfluid lines. In additional embodiments thereof, the fourth embodimentsinclude ones in which the controller establishes the equal flowsthroughout the fixed volume channel for a predefined interval. Inadditional embodiments thereof, the fourth embodiments include ones inwhich the controller derives the at least one control parameter withoutestablishing equal flows throughout the fixed volume channel by fittinga hydraulic model to dynamic data from at least one sensor of thesensors. In additional embodiments thereof, the fourth embodimentsinclude ones in which during the synchronization mode, the controllerdirectly measures a flow rate generated by at least one of the first andsecond pumping actuators to generate a flow rate parameter, the at leastone control parameter includes data responsive to the flow rateparameter. In additional embodiments thereof, the fourth embodimentsinclude ones in which the first fluid lines engage third and fourthpumping actuators, respectively, the third and fourth pumping actuatorsare halted during the synchronization mode to prevent flow in the one ofthe first fluid lines.

According to fifth embodiments, the disclosed subject matter includes,an apparatus for controlling flow in a fluid circuit. A treatmentmachine with flow regulators and sensors, the flow regulators includespumping actuators includes first and second pumping actuators. Thetreatment machine has a controller connected to control the flowregulators and receive signals from the sensors to implement atherapeutic treatment by regulates the flow of blood and treatment fluidwhen a predefined fluid circuit is connected in operative engagementwith the flow regulators and sensors. The predefined fluid circuit has aplurality of fluid lines includes first and second fluid lines allinterconnected by a treatment device of the fluid circuit, each of thefluid lines are used to transport a fluid during the treatment mode inorder to implement the therapeutic treatment. The treatment device has afirst compartment connected to the first fluid lines and a secondcompartment connected to the second fluid lines, the first and secondcompartments are connected for flow therebetween. The flow regulatorsare controlled by the controller, at a first time during asynchronization mode thereof, to selectively block flow in the secondfluid lines by halting the first and second pumping actuators whileselectively pumping fluid through the first fluid lines at a first flowrate and storing first data responsive to a pressure signal from thesensors indicating a pressure of the first or second compartment. Theflow regulators are controlled by the controller, at a second time,during the synchronization mode, to regulate the relative speeds of thefirst and second pumping actuators responsively to the pressure signalto estimate commanded rates of the first and second pumping actuatorseffective to bring about a predefined relationship between the firstdata and the pressure signal and to calculate and record at least onefirst control parameter indicating a relationship between the speeds ofthe first and second pumping actuators when the predefined relationshipexists at the first flow rate. The controller controls the first andsecond pumping actuators responsively to the at least one first controlparameter to implement a predefined ratio of flow rates during atreatment mode.

In additional embodiments thereof, the fifth embodiments include ones inwhich the predefined relationship is equality of pressures indicated bythe pressure signal and the first data. In additional embodimentsthereof, the fifth embodiments include ones in which the flow regulatorsare controlled by the controller, at a third time during thesynchronization mode thereof, to selectively block flow in the secondfluid lines by halting the first and second pumping actuators whileselectively pumping fluid through the first fluid lines at a second flowrate and to store second data responsive to the pressure signal. Theflow regulators are controlled by the controller, at a fourth time,during the synchronization mode, to regulate the relative speeds of thefirst and second pumping actuators responsively to the pressure signalto estimate commanded rates of the first and second pumping actuatorseffective to bring about the predefined relationship between the seconddata and the pressure signal and to calculate and record at least onesecond control parameter indicating a relationship between the speeds ofthe first and second pumping actuators when the predefined relationshipexists at the second flow rate. The controller calculates at least onethird control parameter responsive to the at least one first and atleast one second control parameters and controlling the first and secondpumping actuators responsively to the third control parameter to cause apredefined ratio of flow rates, during a treatment mode, in the secondfluid lines.

In additional embodiments thereof, the fifth embodiments include ones inwhich the first or second compartment is the first compartment. Inadditional embodiments thereof, the fifth embodiments include ones inwhich the first or second compartment is the second compartment. Inadditional embodiments thereof, the fifth embodiments include ones inwhich some of the first and second fluid lines are interconnected by thetreatment device. In additional embodiments thereof, the fifthembodiments include ones in which the first fluid lines are blood linesand the second lines are medicament lines. In additional embodimentsthereof, the fifth embodiments include ones in which the second fluidlines are blood lines and the first fluid lines are medicament lines. Inadditional embodiments thereof, the fifth embodiments include ones inwhich at least one of the fluid lines is connected to a containerstoring a drug. In additional embodiments thereof, the fifth embodimentsinclude ones in which at least one of the fluid lines is connected to acontainer storing a replacement fluid. In additional embodimentsthereof, the fifth embodiments include ones in which the treatmentdevice is a dialyzer and the second fluid lines are fresh dialysate linewaste dialysate fluid lines, respectively. In additional embodimentsthereof, the fifth embodiments include ones in which the first andsecond fluid lines are interconnected by a treatment device, the secondfluid lines are blood lines and the first and second pumping actuatorsare fresh and waste treatment fluid blood pumping actuators. Inadditional embodiments thereof, the fifth embodiments include ones inwhich the first fluid lines are separated from the second fluid lines bya membrane of the treatment device which permits flow of at least watertherethrough. In additional embodiments thereof, the fifth embodimentsinclude ones in which pressure data corresponding to the pressuresignals are recorded during the synchronization mode and included in theat least one first control parameter, the pressure signals are used bythe controller to generate a commanded speed of at least one of thefirst and second pumping actuators to account for differences betweenthe pressure data and pressure signals during the synchronization modeand the treatment mode. In additional embodiments thereof, the fifthembodiments include ones in which the first and second fluid lines areinterconnected by a treatment device, the second fluid lines are bloodlines and the first and second pumping actuators are fresh and wastetreatment fluid blood pumping actuators. In additional embodimentsthereof, the fifth embodiments include ones in which the first fluidlines are separated from the second fluid lines by a membrane of thetreatment device which permits flow of at least water therethrough. Inadditional embodiments thereof, the fifth embodiments include ones inwhich pressure data corresponding to the pressure signal are recordedduring the synchronization mode and included in the at least one thirdcontrol parameter, the pressure signals are used by the controller togenerate a commanded speed of at least one of the first and secondpumping actuators to account for differences between the pressure dataand pressure signals during the synchronization mode and the treatmentmode. In additional embodiments thereof, the fifth embodiments includeones in which at least one of the fluid lines is connected to acontainer storing a drug. In additional embodiments thereof, the fifthembodiments include ones in which at least one of the fluid lines isconnected to a container storing a replacement fluid. In additionalembodiments thereof, the fifth embodiments include ones in which thetreatment device is a dialyzer and the second fluid lines are freshdialysate line waste dialysate fluid lines, respectively. In additionalembodiments thereof, the fifth embodiments include ones in which thefirst and second fluid lines are interconnected by a treatment device,the second fluid lines are blood lines and the first and second pumpingactuators are fresh and waste treatment fluid blood pumping actuators.In additional embodiments thereof, the fifth embodiments include ones inwhich the first fluid lines are separated from the second fluid lines bya membrane of the treatment device which permits flow of at least watertherethrough. In additional embodiments thereof, the fifth embodimentsinclude ones in which pressure data corresponding to the pressuresignals are recorded during the synchronization mode and included in theat least one first control parameter, the pressure signals are used bythe controller to generate a commanded speed of at least one of thefirst and second pumping actuators to account for differences betweenthe pressure data and pressure signals during the synchronization modeand the treatment mode. In additional embodiments thereof, the fifthembodiments include ones in which the first and second fluid lines areinterconnected by a treatment device, the second fluid lines are bloodlines and the first and second pumping actuators are fresh and wastetreatment fluid blood pumping actuators. In additional embodimentsthereof, the fifth embodiments include ones in which the first fluidlines are separated from the second fluid lines by a membrane of thetreatment device which permits flow of at least water therethrough. Inadditional embodiments thereof, the fifth embodiments include ones inwhich pressure data corresponding to the pressure signal are recordedduring the synchronization mode and included in the at least one thirdcontrol parameter, the pressure signals are used by the controller togenerate a commanded speed of at least one of the first and secondpumping actuators to account for differences between the pressure dataand pressure signals during the synchronization mode and the treatmentmode. In additional embodiments thereof, the fifth embodiments includeones in which the first and second flow rates are selected to be typicalof flow rates during the treatment mode. In additional embodimentsthereof, the fifth embodiments include ones in which the at least onethird control parameter are parameters of a function or lookup tablefitted to speed and pressure data. In additional embodiments thereof,the fifth embodiments include ones in which wherein: the controller isconnected to a flow restrictor that permits the pressure in the first orsecond compartment to be controlled by the controller when a flow isestablished therethrough, and the controller generates additionalcontrol parameters responsively various combinations and pressures andflows in the first or second compartment which are used by thecontroller to calculate the third control parameter. In additionalembodiments thereof, the fifth embodiments include ones in which thecontroller reestablishes the synchronization mode responsively to anevent after first establishing the treatment mode, and thenreestablishes the treatment mode with a new at least one first controlparameter. In additional embodiments thereof, the fifth embodimentsinclude ones in which the event includes a lapse of a predefinedinterval of time since an initial establishment of the treatment mode.In additional embodiments thereof, the fifth embodiments include ones inwhich the predefined ratio is responsive to a predefined ultrafiltrationrate and the event includes a change in the predefined ultrafiltratonrate. In additional embodiments thereof, the fifth embodiments includeones in which wherein the first fluid lines are blood lines and thesecond lines are medicament lines or the second fluid lines are bloodlines and the first lines are medicament lines, wherein the eventincludes a change pressure in at least one of the blood lines. Inadditional embodiments thereof, the fifth embodiments include ones inwhich the first fluid lines are blood lines and the second lines aremedicament lines or the second fluid lines are blood lines and the firstlines are medicament lines, wherein the event includes a change pressurein at least one of the medicament lines. In additional embodimentsthereof, the fifth embodiments include ones in which the event includesthe receipt by the controller of a command from a user interface toreestablish the synchronization mode. In additional embodiments thereof,the fifth embodiments include ones in which the event includes thecompletion of an alarm and recover mode during which the treatment modewas stopped for at least a predefined period of time. In additionalembodiments thereof, the fifth embodiments include ones in which theevent includes a change in absolute flow rate generated by at least onethe first and second pumping actuators. In additional embodimentsthereof, the fifth embodiments include ones in which the event includesthe reestablishment of the treatment mode after a stoppage for thechange of a component of the fluid circuit. In additional embodimentsthereof, the fifth embodiments include ones in which the controllerreestablishes the synchronization mode responsively to an event afterfirst establishing the treatment mode, and then reestablishes thetreatment mode with a new at least one first control parameter. Inadditional embodiments thereof, the fifth embodiments include ones inwhich the event includes a lapse of a predefined interval of time sincean initial establishment of the treatment mode. In additionalembodiments thereof, the fifth embodiments include ones in which thepredefined ratio is responsive to a predefined ultrafiltration rate andthe event includes a change in the predefined ultrafiltraton rate. Inadditional embodiments thereof, the fifth embodiments include ones inwhich the first fluid lines are blood lines and the second lines aremedicament lines or the second fluid lines are blood lines and the firstlines are medicament lines, wherein the event includes a change pressurein at least one of the blood lines. In additional embodiments thereof,the fifth embodiments include ones in which the first fluid lines areblood lines and the second lines are medicament lines or the secondfluid lines are blood lines and the first lines are medicament lineswherein the event includes a change pressure in at least one of themedicament lines. In additional embodiments thereof, the fifthembodiments include ones in which the event includes the receipt by thecontroller of a command from a user interface to reestablish thesynchronization mode. In additional embodiments thereof, the fifthembodiments include ones in which the event includes the completion ofan alarm and recover mode during which the treatment mode was stoppedfor at least a predefined period of time. In additional embodimentsthereof, the fifth embodiments include ones in which the event includesa change in absolute flow rate generated by at least one the first andsecond pumping actuators. In additional embodiments thereof, the fifthembodiments include ones in which the event includes the reestablishmentof the treatment mode after a stoppage for the change of a component ofthe fluid circuit. In additional embodiments thereof, the fifthembodiments include ones in which the synchronization mode occurs duringpriming of a blood circuit in advance of the treatment mode. Inadditional embodiments thereof, the fifth embodiments include ones inwhich the first flow rate is equal to a rate prescribed for flow throughthe first fluid lines during the treatment mode. In additionalembodiments thereof, the fifth embodiments include ones in which thespeeds of the first and second pumping actuators are responsive to atreatment fluid flow rate prescribed for flow through second fluid linesduring the treatment mode. In additional embodiments thereof, the fifthembodiments include ones in which the speeds of the first and secondpumping actuators are responsive to a treatment fluid flow rateprescribed for flow through second fluid lines during the treatmentmode. In additional embodiments thereof, the fifth embodiments includeones in which the first flow rate is equal to a rate prescribed for flowthrough the first fluid lines during the treatment mode. In additionalembodiments thereof, the fifth embodiments include ones in which thespeeds of the first and second pumping actuators are responsive to atreatment fluid flow rate prescribed for flow through second fluid linesduring the treatment mode. In additional embodiments thereof, the fifthembodiments include ones in which the speeds of the first and secondpumping actuators are responsive to a treatment fluid flow rateprescribed for flow through second fluid lines during the treatmentmode. In additional embodiments thereof, the fifth embodiments includeones in which the controller stores a difference in pressure between thefirst and second compartments that exists at at least one of the firstand second times and outputs the difference in pressure as an indicationof oncotic pressure. In additional embodiments thereof, the fifthembodiments include ones in which controller stores a difference inpressure between the first and second compartments that exists at atleast one of the first and second times, the controller calculating thefirst control parameter responsively top the difference in pressure. Inadditional embodiments thereof, the fifth embodiments include ones inwhich the controller stores a difference in pressure between the firstand second compartments that exists at at least one of the first andsecond times, calculates a diagnostic parameter responsive to thedifference in pressure and outputs the diagnostic parameter. Inadditional embodiments thereof, the fifth embodiments include ones inwhich the diagnostic parameter includes a patient's blood hematocrit. Inadditional embodiments thereof, the fifth embodiments include ones inwhich the diagnostic parameter includes a patient's water level.

According to sixth embodiments, the disclosed subject matter includes, amethod for controlling fluid flow in a fluid circuit. The methodincludes connecting first inflow and outflow lines to one of blood andnon-blood compartments of a blood treatment device. The method includesconnecting second inflow and outflow lines to the other of blood andnon-blood compartments of the blood treatment device. The methodincludes using a controller, regulating a speed of a first inflow pump,connected to the first inflow line, to establish a flow into the one ofblood and non-blood compartments of a blood treatment device. The methodincludes regulating a speed of a first outflow pump connected to thefirst outflow line to establish a flow out of the one of blood andnon-blood compartments of a blood treatment device and detecting apressure of at least one of the blood and non-blood compartments, thepressure indicating a magnitude of a difference between the rates of theflows into and out of the one of blood and non-blood compartments. Themethod includes calculating a flow control parameter responsively to thepressure. The method includes thereafter regulating a net transfer offluid between the blood and non-blood compartments responsively to thecontrol parameter.

In additional embodiments thereof, the sixth embodiments include onesthat further include, during the detecting, flowing fluid through thesecond inflow and outflow lines.

In additional embodiments thereof, the sixth embodiments include onesthat further include, during the detecting, blocking the flow of fluidthrough the second inflow and outflow lines such that the first inflowand outflow lines and the one of blood and non-blood compartments of ablood treatment device constitute a fixed volume fluid channel.

In additional embodiments thereof, the sixth embodiments include ones inwhich the pressure indicates a magnitude of a transmembrane transportbetween the blood and non-blood compartments. In additional embodimentsthereof, the sixth embodiments include ones in which, wherein thepressure indicates a magnitude of a transmembrane transport between theblood and non-blood compartments and the calculating includes comparingthe pressure to a predefined threshold pressure indicative of zeromagnitude of a transmembrane transport between the blood and non-bloodcompartments. In additional embodiments thereof, the sixth embodimentsinclude ones in which the pressure indicates a magnitude of atransmembrane transport between the blood and non-blood compartments.The calculating includes comparing the pressure to a predefinedthreshold pressure indicative of zero magnitude of a transmembranetransport between the blood and non-blood compartments. The variation ofthe method further includes determining the predefined thresholdpressure by detecting a pressure of the at least one of the blood andnon-blood compartments while blocking transport between the blood andnon-blood compartments.

In additional embodiments thereof, the sixth embodiments include ones inwhich the pressure indicates a magnitude of a transmembrane transportbetween the blood and non-blood compartments. The calculating includescomparing the pressure to a predefined threshold pressure indicative ofzero magnitude of a transmembrane transport between the blood andnon-blood compartments. The method further includes determining thepredefined threshold pressure by detecting a pressure of the at leastone of the blood and non-blood compartments while blocking transportbetween the blood and non-blood compartments and while establishing flowthrough the second inflow and outflow lines at a predefined flow rate.In additional embodiments thereof, the sixth embodiments include ones inwhich the controller includes an embedded computer with a data store hasinstructions readable thereby to regulate, detect, and calculate and tostore data responsive thereto. In additional embodiments thereof, thesixth embodiments include ones in which the control parameter includes aconstant of proportionality that relates a command speed of a slave pumpto a command speed of a master pump coinciding with identical flow ratestherethrough. In additional embodiments thereof, the sixth embodimentsinclude ones in which the controller adjusts the first outflow pump inresponse to a predefined ultrafiltration flow rate and the controlparameter such that the first outflow pump generates a flow rate that ishigher than that of the first inflow pump. In additional embodimentsthereof, the sixth embodiments include ones in which the controllercontinuously updates a speed of the first outflow pump in response to asignal from the pressure. In additional embodiments thereof, the sixthembodiments include ones in which the pressure of at least one of theblood and non-blood compartments is indicated by a pressure in the firstinflow line and/or a pressure in the first outflow line. In additionalembodiments thereof, the sixth embodiments include ones in which thepressure signal is an average of a pressure in the first inflow line anda pressure in the first outflow line.

According to seventh embodiments, the disclosed subject matter includesa system for controlling fluid flow in a fluid circuit. A bloodtreatment machine has a controller, the controller is programmable isconnected to control a flow control device, a first inflow pump, a firstoutflow pump and a second inflow pump, and to receive pressure signalsfrom at least one pressure sensor. The first inflow and outflow pumpsare engaged with first inflow and outflow lines, respectively, to flowfluid into and out from one of blood and non-blood compartments of ablood treatment device. The second inflow pump is engaged with a secondinflow line to flow fluid into the other of the blood and non-bloodcompartments and the flow control device are engaged with a secondoutflow line connected to flow fluid out of the other of the blood andnon-blood compartments. The controller is connected to at least onepressure sensor that generates a pressure signal indicating a pressureinside at least one of the blood and non-blood compartments, thepressure indicating a magnitude of a difference between the rates of theflows into and out of the one of blood and non-blood compartments. Thecontroller is programmed to, in a synchronization mode, (1) regulate aspeed of a first outflow pump connected to the first outflow line toestablish a flow out of the one of blood and non-blood compartments of ablood treatment device; and (2) use the pressure signal to calculate aflow control parameter of the first outflow pump responsively to thepressure. The controller is further programmed to, thereafter, in atreatment mode regulate a net transfer of fluid between the blood andnon-blood compartments responsively to the control parameter.

In additional embodiments thereof, the seventh embodiments include onesthat further include, during the detecting, flowing fluid through thesecond inflow and outflow lines.

In additional embodiments thereof, the seventh embodiments include onesthat further include, during the detecting, blocking the flow of fluidthrough the second inflow and outflow lines such that the first inflowand outflow lines and the one of blood and non-blood compartments of ablood treatment device constitute a fixed volume fluid channel.

In additional embodiments thereof, the seventh embodiments include onesin which the pressure indicates a magnitude of a transmembrane transportbetween the blood and non-blood compartments. In additional embodimentsthereof, the seventh embodiments include ones in which the pressureindicates a magnitude of a transmembrane transport between the blood andnon-blood compartments and the calculating includes comparing thepressure to a predefined threshold pressure indicative of zero magnitudeof a transmembrane transport between the blood and non-bloodcompartments. In additional embodiments thereof, the seventh embodimentsinclude ones in which the pressure indicates a magnitude of atransmembrane transport between the blood and non-blood compartments.The calculating includes comparing the pressure to a predefinedthreshold pressure indicative of zero magnitude of a transmembranetransport between the blood and non-blood compartments. The systemfurther includes determining the predefined threshold pressure bydetecting a pressure of the at least one of the blood and non-bloodcompartments while blocking transport between the blood and non-bloodcompartments.

In additional embodiments thereof, the seventh embodiments include onesin which the pressure indicates a magnitude of a transmembrane transportbetween the blood and non-blood compartments. The calculating includescomparing the pressure to a predefined threshold pressure indicative ofzero magnitude of a transmembrane transport between the blood andnon-blood compartments. The system further includes determining thepredefined threshold pressure by detecting a pressure of the at leastone of the blood and non-blood compartments while blocking transportbetween the blood and non-blood compartments and while establishing flowthrough the second inflow and outflow lines at a predefined flow rate.In additional embodiments thereof, the seventh embodiments include onesin which the controller includes an embedded computer with a data storehas instructions readable thereby to regulate, detect, and calculate andto store data responsive thereto. In additional embodiments thereof, theseventh embodiments include ones in which the control parameter includesa constant of proportionality that relates a command speed of a slavepump to a command speed of a master pump coinciding with identical flowrates therethrough. In additional embodiments thereof, the seventhembodiments include ones in which the controller is further programmedto, adjust the first outflow pump in response to a predefinedultrafiltration flow rate and the control parameter such that the firstoutflow pump generates a flow rate that is higher than that of the firstinflow pump. In additional embodiments thereof, the seventh embodimentsinclude ones in which the controller is further programmed to, in thetreatment mode, continuously update a speed of the first outflow pump inresponse to a signal from the pressure. In additional embodimentsthereof, the seventh embodiments include ones in which at least onepressure sensor is at least two, one of which indicates a pressure inthe first inflow line and another of which indicates a pressure of thefirst outflow line. In additional embodiments thereof, the seventhembodiments include ones in which the pressure signal is an average ofsignals from the at least two.

According to eighth embodiments, the disclosed subject matter includes amethod for controlling flow in a blood treatment fluid circuit. Themethod includes pumping fluid serially through first fluid linesconnected to second fluid lines through a blood treatment device whileblocking flow through the second fluid lines. The pumping includes,using a controller to control the speeds of pumping actuators, each ofthe pumping actuators determining a flow rate through a respective oneof the first fluid lines. The first fluid lines are one of blood linesand treatment fluid lines and the second lines are the other of bloodlines and treatment fluid lines. The method includes using thecontroller, detecting sensor data indicating a difference between theflow rates in the first fluid lines as well as speed data indicating aspeed of at least one of the pumping actuators. The method includesusing the controller, calculating one or more control parameters fromthe speed and sensor data, the one or more control parameters indicatingthe speed of the at least one of the pumping actuators for which thedifference is below a predefined threshold. The method includes usingthe controller, regulating a net transfer of fluid through the firstfluid line pair to, or from, the blood treatment device by regulates thespeeds of the at least one of the pumping actuators responsively to theone or more control parameters.

In additional embodiments thereof, the eighth embodiments include onesin which the detecting and calculating are performed during asynchronization mode and the regulates is performed during a treatmentmode. In additional embodiments thereof, the eighth embodiments includeones in which the calculating includes feedback controlling the at leastone of the pumping actuators responsively to the sensor data to achievea target magnitude indicated by the sensor data.

In additional embodiments thereof, the eighth embodiments include onesin which the sensor data is from a digitized pressure sensor signal, thepressure sensor indicating the pressure inside the blood treatmentdevice.

In additional embodiments thereof, the eighth embodiments include onesin which the second fluid lines are blood lines of a hemodialysis fluidcircuit. In additional embodiments thereof, the eighth embodimentsinclude ones in which the blood treatment device is a dialyzer. Inadditional embodiments thereof, the eighth embodiments include ones inwhich the regulates includes a net transfer of fluid responsively toboth the one or more control parameters and a predefined ultrafiltrationrate, such that a net flow from the blood treatment device through thefirst fluid lines, equal to the predefined ultrafiltration rate, isestablished.

According to ninth embodiments, the disclosed subject matter includes asystem for controlling flow in a blood treatment fluid circuit. A bloodtreatment machine is engaged with a fluid circuit has first and secondfluid lines pairs connected to a blood treatment device. The bloodtreatment machine has a sensor that generates sensor data indicating adifference between the flow rates in the first fluid line pair. Theblood treatment machine has a controller connected to the sensor,pumping actuators that pump fluid through the first and second linepairs and one line of the second fluid line pairs, and a flow regulatorthat controls flow through the other line of the second fluid linepairs. The controller pumps fluid serially through first fluid line pairconnected to second fluid lines through a blood treatment device whileblocking flow through the second fluid line pair. The first fluid linesare one of blood lines and treatment fluid lines and the second linesare the other of blood lines and treatment fluid lines. The controllerdetects the sensor data as well as speed data indicating a speed of atleast one of the pumping actuators. The controller calculates one ormore control parameters from the speed and the sensor data, the one ormore control parameters indicating a speed of the at least one of thepumping actuators for which the difference is below a predefinedthreshold. The controller regulates a net transfer of fluid through thefirst fluid line pair to, or from, the blood treatment device byregulates the speeds of the at least one of the pumping actuatorsresponsively to the one or more control parameters.

In additional embodiments thereof, the ninth embodiments include ones inwhich the detecting and calculating are performed during asynchronization mode and the regulates is performed during a treatmentmode. In additional embodiments thereof, the ninth embodiments includeones in which the calculating includes feedback controlling the at leastone of the pumping actuators responsively to the sensor data to achievea target magnitude indicated by the sensor data. In additionalembodiments thereof, the ninth embodiments include ones in which,wherein the sensor data is from a digitized pressure sensor signal, thepressure sensor indicating the pressure inside the blood treatmentdevice. In additional embodiments thereof, the ninth embodiments includeones in which, the second fluid lines are blood lines of a hemodialysisfluid circuit. In additional embodiments thereof, the ninth embodimentsinclude ones in which the blood treatment device is a dialyzer. Inadditional embodiments thereof, the ninth embodiments include ones inwhich the regulates includes a net transfer of fluid responsively toboth the one or more control parameters and a predefined ultrafiltrationrate, such that a net flow from the blood treatment device through thefirst fluid lines, equal to the predefined ultrafiltration rate, isestablished. In additional embodiments thereof, the ninth embodimentsinclude ones in which the predefined threshold is a pressure in theblood treatment device when there is no flow in the first fluid linepair. In additional embodiments thereof, the ninth embodiments includeones in which the first fluid line pair is connected to a source andcollector of dialysate.

According to tenth embodiments, the disclosed subject matter includes amethod for controlling flow in a fluid circuit. The method applies to ablood treatment system that regulates the net ultrafiltration of apatient by balancing fluid withdrawn from a blood treatment deviceagainst fluid pump into the blood treatment device by controlling therelative volume displaced during a treatment by independently-regulatedinflow and outflow pumps. The method includes using a controller, duringa testing mode, detecting a difference between the flow rates of theinflow and outflow pumps continuously over a test interval while storingdifference data representing the difference over time. The methodincludes using the controller, while detecting the difference andgenerating the difference data, controlling the rate of at least one ofthe inflow and outflow pumps to minimize the difference withoutestablishing a minimum of the difference. The method includescalculating, from the difference data and the rate of the at least oneof the inflow and outflow pumps, a control parameter for regulates theat least one of the inflow and outflow pumps by extrapolating from atrend in the difference data an equilibrium rate of the at least one ofthe inflow and outflow pumps that corresponds to a minimum of thedifference. The method includes performing a treatment includescontrolling a net flow of fluid to or from a patient by controlling theinflow and outflow volumetric pumps responsively to the controlparameter.

In additional embodiments thereof, the tenth embodiments include ones inwhich the blood treatment system is a dialysis system. In additionalembodiments thereof, the tenth embodiments include ones in which the atleast one of the inflow and outflow pumps pump fresh dialysate and spentdialysate, respectively. In additional embodiments thereof, the tenthembodiments include ones in which the calculating includes calculating atime-resolved moving average from the difference data and fitting thetime-resolved moving average to a curve of flow difference vs. time.

According to eleventh embodiments, the disclosed subject matter includesa system for controlling flow in a fluid circuit. A blood treatmentsystem that regulates the net ultrafiltration of a patient by balancingfluid withdrawn from a blood treatment device against fluid pump intothe blood treatment device by controlling the relative volume displacedduring a treatment by independently-regulated inflow and outflow pumps.A controller has a sensor adapted for indicating a difference betweenthe flow rates of the inflow and outflow pumps. The controller, during atesting mode, detects a difference between the flow rates of the inflowand outflow pumps continuously over a test interval while storingdifference data representing the difference over time. The controller,while detecting the difference and generating the difference data,controls the rate of at least one of the inflow and outflow pumps tominimize the difference without establishing a minimum of thedifference. The controller calculates, from the difference data and therate of the at least one of the inflow and outflow pumps, a controlparameter for regulates the at least one of the inflow and outflow pumpsby extrapolating from a trend in the difference data an equilibrium rateof the at least one of the inflow and outflow pumps that corresponds toa minimum of the difference. The controller performs a treatmentincludes controlling a net flow of fluid to or from a patient bycontrolling the inflow and outflow volumetric pumps responsively to thecontrol parameter.

In additional embodiments thereof, the eleventh embodiments include onesin which the blood treatment system is a dialysis system. In additionalembodiments thereof, the eleventh embodiments include ones in which theat least one of the inflow and outflow pumps pump fresh dialysate andspent dialysate, respectively. In additional embodiments thereof, theeleventh embodiments include ones in which the calculating includescalculating a time-resolved moving average from the difference data andfitting the time-resolved moving average to a curve of flow differencevs. time.

According to twelfth embodiments, the disclosed subject matter includesa blood treatment machine. Inflow and outflow pump actuators and atleast one pressure sensor are connectable to a fluid circuit formeasuring a pressure in a connected fluid circuit has a blood treatmentdevice a controller, the pressure sensor indicating a difference betweenthe flow rates of the inflow and outflow pump actuators. A controllerregulates the inflow and outflow pump actuators to achieve a selectednet ultrafiltration of a patient by balancing fluid withdrawn from ablood treatment device against fluid pump into the blood treatmentdevice by independently regulates the speeds of the inflow and outflowpump actuators to achieve a relative volume displaced during a treatmentby the inflow and outflow pump actuators. The controller, during atesting mode, detects a difference between the flow rates of the inflowand outflow pumps continuously over a test interval while storingdifference data representing the difference over time. The controller,while detecting the difference and generating the difference data,controls the rate of at least one of the inflow and outflow pumpactuators to minimize the difference without establishing a minimum ofthe difference. The controller calculates, from the difference data andthe rate of the at least one of the inflow and outflow pump actuators, acontrol parameter for regulating the at least one of the inflow andoutflow pump actuators by extrapolating from a trend in the differencedata an equilibrium rate of the at least one of the inflow and outflowpump actuators that corresponds to a predetermined constant magnitude ofa pressure indicated by the pressure sensor. The controller controls anet flow of fluid to or from a patient by controlling the inflow andoutflow volumetric pumps responsively to the control parameter.

In additional embodiments thereof, the twelfth embodiments include onesin which the blood treatment machine is a dialysis cycler. In additionalembodiments thereof, the twelfth embodiments include ones in which thecalculating includes calculating a time-resolved moving average from thedifference data and fitting the time-resolved moving average to a curveof flow difference vs. time.

According to thirteenth embodiments, the disclosed subject matterincludes a method for controlling flow in a fluid circuit. The methodincludes, using the controller, establishing a blood flow in a bloodtreatment device with a membrane, at a predefined rate while preventingtransmembrane flow across the membrane and detecting and storing atarget pressure equal to a detected pressure within the blood treatmentdevice. The method includes, during a synchronization mode, using thecontroller, feedback-controlling the speed of one or both of the inflowand outflow treatment fluid pumps responsively to a difference betweenthe target pressure and a detected pressure inside the blood treatmentdevice and calculating a control parameter from a resulting speed of theone or both of the inflow and outflow treatment fluid pumps, the controlparameter indicating a relationship between the relative speeds of theinflow and outflow treatment fluid pumps under a condition of zerotransmembrane flow. The method includes, during a treatment mode, usingthe controller, regulates the flow of treatment fluid across through theblood treatment device by regulates the relative speeds of the inflowand outflow treatment fluid pumps responsively to the control parameter.

In additional embodiments thereof, the thirteenth embodiments includeones in which the feedback-controlling includes controlling the inlettreatment fluid pump responsive to a difference between the targetpressure and a detected pressure in the blood treatment device. Inadditional embodiments thereof, the thirteenth embodiments include onesin which the preventing includes halting the inflow and outflowtreatment fluid pumps to prevent flow of treatment fluid through theblood treatment device. In additional embodiments thereof, thethirteenth embodiments include ones in which the inflow and outflowtreatment fluid pumps include peristaltic pumps. In additionalembodiments thereof, the thirteenth embodiments include ones in which,the detecting a target pressure includes receiving and averagingpressure signals from pressure sensors connected to detect the pressuresof respective fluid lines between the inflow and outflow treatment fluidpumps and the blood treatment device. In additional embodiments thereof,the thirteenth embodiments include ones in which the detecting a targetpressure includes receiving a pressure signal from a pressure sensorconnected to detect the pressure of a fluid line between one of theinflow and outflow treatment fluid pumps and the blood treatment device.

In additional embodiments thereof, the thirteenth embodiments includeones in which the detected pressure is indicated by a pressure sensorindicating a pressure on a treatment fluid side of the membrane. Inadditional embodiments thereof, the thirteenth embodiments include onesin which the regulates the relative speeds of the inflow and outflowtreatment fluid pumps responsively to the control parameter includesestablishing a speed of the outflow treatment fluid pump that is greaterthan a speed corresponding to the control parameter and responsive to apredefined ultrafiltration rate. In additional embodiments thereof, thethirteenth embodiments include ones in which the regulates the relativespeeds of the inflow and outflow treatment fluid pumps responsively tothe control parameter includes establishing a speed of the outflowtreatment fluid pump that is greater than a speed corresponding to thecontrol parameter by an amount that is proportional to a predefinedultrafiltration rate.

In additional embodiments thereof, the thirteenth embodiments includeones that include adjusting a speed of the outflow treatment fluid pumpresponsively to an inlet pressure thereof in order to maintain aconstant flow therethrough, the outflow treatment fluid pump are of atype whose volume rate of flow, for a given speed, is affected by inletpressure.

According to fourteenth embodiments, the disclosed subject matterincludes a device for controlling flow in a fluid circuit. First andsecond fluid circuits are coupled by an exchange device in which thefirst and second fluid circuits are separated by a membrane. Tcontroller controls transmembrane flow between the first or second fluidcircuits by regulates the rate of flow into the exchange device throughthe first fluid circuit by controlling the speed of a first pumprelative to the rate out of the exchange device through the first fluidcircuit by controlling the speed of a second pump. At a first time, thecontroller establishes a flow the second fluid circuit while preventinga transmembrane flow across the membrane and detecting and storing atarget pressure equal to a detected pressure within the exchange device.At a second time, after the first time, the controller feedback-controlsthe speeds of one or both of the first and second pumps responsively toa difference between the target pressure and a detected pressure insidethe exchange device and calculating a control parameter from a resultingspeed of the one or both of the inflow and outflow treatment fluidpumps, the control parameter indicating a relationship between therelative speeds of the inflow and outflow treatment fluid pumps under acondition of zero transmembrane flow. The controller thereafterregulates controlling transmembrane flow between the first or secondfluid circuits responsively to the control parameter.

In additional embodiments thereof, the fourteenth embodiments includeones in which the feedback-controlling includes controlling the inlettreatment fluid pump responsive to a difference between the targetpressure and a detected pressure in exchange device. In additionalembodiments thereof, the fourteenth embodiments include ones in whichthe preventing includes halting the first and second pumps to preventflow of fluid in the first circuit. In additional embodiments thereof,the fourteenth embodiments include ones in which the first and secondpumps include peristaltic pumps.

In additional embodiments thereof, the fourteenth embodiments includeones in which the feedback-controlling includes receiving and averagingpressure signals from pressure sensors connected to detect the pressuresof respective fluid lines between the first and second pumps and theexchange device. In additional embodiments thereof, the fourteenthembodiments include ones in which the detecting a target pressureincludes receiving a pressure signal from a pressure sensor connected todetect the pressure of a fluid line between one of the first and secondpumps and the exchange device.

In additional embodiments thereof, the fourteenth embodiments includeones in which the detecting a target pressure includes receiving apressure signal indicating a pressure on a treatment fluid side of themembrane. In additional embodiments thereof, the fourteenth embodimentsinclude ones in which the regulates the relative speeds of the inflowand outflow treatment fluid pumps responsively to the control parameterincludes establishing a speed of the outflow treatment fluid pump thatis greater than a speed corresponding to the control parameter andresponsive to a predefined ultrafiltration rate. In additionalembodiments thereof, the fourteenth embodiments include ones in whichthe regulates the relative speeds of the inflow and outflow treatmentfluid pumps responsively to the control parameter includes establishinga speed of the outflow treatment fluid pump that is greater than a speedcorresponding to the control parameter by an amount that is proportionalto a predefined ultrafiltration rate.

In additional embodiments thereof, the fourteenth embodiments includeones that include adjusting a speed of the second pump responsively toan inlet pressure thereof in order to maintain a constant flowtherethrough, the second pump are of a type whose volume rate of flow,for a given speed, is affected by its inlet pressure.

According to fifteenth embodiments, the disclosed subject matterincludes, a system for controlling flow in a fluid circuit. A treatmentmachine has a fluid circuit engaged with first, second, and thirdpumping actuators. The treatment machine has a controller connected tocontrol the first, second, and third pumping actuators to perform atherapeutic treatment by regulates the flow fluid in a fluid circuit.The fluid circuit has a treatment device that interconnects first fluidlines via a first compartment thereof and second fluid lines via asecond compartment thereof, the first and second pumping actuatorscontrolling a net transport of fluid between the first and secondcompartments during a treatment mode, the pressure sensor indicating apressure of the first and/or second compartment. The first, second, andthird pumping actuators are controlled by the controller, at a firsttime during a synchronization mode, to block flow in the first fluidlines while pumping fluid through the second compartment at a predefinedflow rate and to simultaneously store target pressure data responsive toa pressure signal from the pressure sensor. The controller determines apump control parameter responsively by feedback-controlling the firstand second pumping actuators toward a control goal based on the targetpressure data and estimating a speed of one or both of the first andsecond pumping actuators that establishes the control goal and anidentical flow rate of the first and second pumps indicated by aconstant pressure signal from the pressure sensor. The first and secondpumping actuators are controlled by the controller, at a second timeduring a treatment mode to pump fluid through the second compartment atthe predefined flow rate while simultaneously controlling flow in thefirst fluid lines responsively to the control parameter.

In additional embodiments thereof, the fifteenth embodiments includeones in which the treatment device is a hemodialyzer and the first andsecond pumping actuators are engaged with dialysate and waste pumpsconnected to the hemodialyzer. In additional embodiments thereof, thefifteenth embodiments include ones in which first compartment is adialysate compartment of a dialyzer. In additional embodiments thereof,the fifteenth embodiments include ones in which second compartment is ablood compartment of a dialyzer. In additional embodiments thereof, thefifteenth embodiments include ones in which the determining includesextrapolating a trend of pressure versus time and estimating therefrom arelationship between the speed of the first pump and the speed of thesecond pump that provide the same flow rates through the first andsecond pumps.

According to sixteenth embodiments, the disclosed subject matterincludes a system for controlling flow in a fluid circuit. A machine hasa fluid circuit engaged with first, second, and third pumping actuators.The treatment machine has a controller connected to control the first,second, and third pumping actuators to regulate a flow fluid in a fluidcircuit. The fluid circuit has a fluid exchange device thatinterconnects first fluid lines via a first compartment thereof andsecond fluid lines via a second compartment thereof, the first andsecond pumping actuators controlling a net transport of fluid betweenthe first and second compartments during production mode, the pressuresensor indicating a pressure of the first and/or second compartment. Thefirst, second, and third pumping actuators are controlled by thecontroller, at a first time during a synchronization mode, to block flowin the first fluid lines while pumping fluid through the secondcompartment at a predefined flow rate and to simultaneously store targetpressure data responsive to a pressure signal from the pressure sensor.The controller determines a pump control parameter responsively byfeedback-controlling the first and second pumping actuators toward acontrol goal based on the target pressure data and estimating a speed ofone or both of the first and second pumping actuators that establishesthe control goal and an identical flow rate of the first and secondpumps indicated by a constant pressure signal from the pressure sensor.The first and second pumping actuators are controlled by the controller,at a second time during the production mode, to pump fluid through thesecond compartment at the predefined flow rate while simultaneouslycontrolling flow in the first fluid lines responsively to the pressuredata.

In additional embodiments thereof, the sixteenth embodiments includeones in which the determining includes extrapolating a trend of pressureversus time and estimating therefrom a relationship between the speed ofthe first pump and the speed of the second pump that provide the sameflow rates through the first and second pumps.

According to seventeenth embodiments, the disclosed subject matterincludes a method for controlling flow in a fluid circuit. The methodincludes regulating the flow of fluid across a blood treatment devicemembrane contacting a blood flow path responsively to a pressure signalresponsive to pressure in the blood treatment device. The regulatingincludes controlling respective speeds of inflow and outflow pumps, theinflow pump pumping treatment fluid into the blood treatment device andthe outflow pump pumping treatment fluid out of the blood treatmentdevice responsively to prediction data correlating pressures on a bloodand/or treatment fluid side of the membrane with flow rates on a bloodside of the membrane. The method further includes, prior to theregulating, detecting pressure signals indicating pressure on the bloodand/or treatment fluid side of the membrane for each of multiple flowrates of fluid on the blood side of the membrane for condition of zeroflow across the membrane and storing the prediction data responsively tothe pressure signals and flow rates.

In additional embodiments thereof, the seventeenth embodiments includeones that include adjusting the outflow pump to draw fluid through themembrane at a predefined ultrafiltration rate. In additional embodimentsthereof, the seventeenth embodiments includes ones in which theregulating includes synchronizing the flow rates inflow and outflowpumps. In additional embodiments thereof, the seventeenth embodimentsincludes ones in which the regulating includes feedback controlling theflow rates inflow and outflow pumps toward a target pressure todetermine rates thereof that produce equal flow.

In additional embodiments thereof, the seventeenth embodiments thatinclude advancing a rate of the outflow pump responsively to apredetermined ultrafiltration rate.

According to eighteenth embodiments, the disclosed subject matterincludes, a system for controlling flow in a fluid circuit. A treatmentmachine has a fluid circuit engaged with first, second, and thirdpumping actuators. The treatment machine has a controller connected tocontrol the first, second, and third pumping actuators to perform atherapeutic treatment by regulates the flow fluid in the fluid circuit.The fluid circuit has a treatment device that interconnects first fluidlines via a first compartment thereof and second fluid lines via asecond compartment thereof, the first and second pumping actuatorscontrolling a net transport of fluid between the first and secondcompartments during a treatment mode, the pressure sensor indicating apressure of the first and/or second compartment. The first and secondpumping actuators are controlled by the controller, at a first timeduring a synchronization mode, to block flow in the first fluid lineswhile pumping fluid through the second compartment at multiplepredefined flow rates and to simultaneously store prediction dataresponsive to a pressure signal from the pressure sensor at each of theflow rates. The first and second pumping actuators are controlled by thecontroller, at a second time during a treatment mode to pump fluidthrough the second compartment at a current flow rate whilesimultaneously controlling flow in the first fluid lines responsively tothe prediction data. In additional embodiments thereof, the eighteenthembodiments includes ones in which the controller, at the second time,adjusts the outflow pump to draw fluid through the membrane at apredefined ultrafiltration rate. In additional embodiments thereof, theeighteenth embodiments includes ones in which the controller, after thefirst time, synchronizes the flow rates inflow and outflow pumps bymonitoring the pressure signal from the pressure sensor to achieve asteady pressure indicated by the pressure sensor at the first time, foreach of the flow rates. In additional embodiments thereof, theeighteenth embodiments includes ones in which the controller, at thesecond time, advances a rate of the outflow pump responsively to apredetermined ultrafiltration rate.

According to nineteenth embodiments, the disclosed subject matterincludes a method for controlling flow in a fluid circuit. The methodincludes treating a patient body fluid by pumping a treatment fluid froma source, through a treatment device, to a sink while pumping the bodyfluid of a patient through the treatment device. The method includesregulating a net transfer of fluid to or from the body fluid bycontrolling the pumping treatment fluid at respective rates into and outof the treatment device. The method includes, at a time before or duringthe treating, isolating the source and sink from the treatment deviceand establishing a closed-loop flow of treatment fluid between anaccumulator and the treatment device while detecting a net transfer offluid through the treatment device and using a result of the detectingto calculate an error in the controlling of the respective rates intoand out of the treatment device. The method includes storing dataindicating the result of the detecting and subsequently furtherregulates a net transfer of fluid to or from the body fluid bycontrolling the pumping treatment fluid at respective rates into and outof the treatment device responsively to the data.

In additional embodiments thereof, the nineteenth embodiments includeones that further include connecting the accumulator with a primingfluid therein to the treatment device. In additional embodimentsthereof, the nineteenth embodiments includes ones in which the detectinga net transfer of fluid through the treatment device includes detectinga change in a weight or volume of the accumulator.

In additional embodiments thereof, the nineteenth embodiments mayinclude reversing a pump to reverse a flow through the accumulator andcollecting air therein. In additional embodiments thereof, thenineteenth embodiments includes ones in which the sink is a collectioncontainer or a drain. In additional embodiments thereof, the nineteenthembodiments includes ones in which the body fluid is blood. Inadditional embodiments thereof, the nineteenth embodiments includes onesin which the treatment fluid is dialysate and the treatment device is adialyzer. In additional embodiments thereof, the nineteenth embodimentsincludes ones in which the regulating includes controlling the relativespeeds of pumps pumping fluid into and out of the treatment device.

According to twentieth embodiments, the disclosed subject matterincludes a system for controlling flow in a fluid circuit. A treatmentmachine has a fluid circuit engaged with a treatment fluid inlet pumpactuator, treatment machine fluid outlet pump actuator, and a blood pumpactuator. The treatment machine has a controller connected to controlthe pumping actuators to perform a therapeutic treatment by regulatesthe flow fluid in the fluid circuit. The fluid circuit has a treatmentdevice that interconnects treatment fluid lines via a non-bloodcompartment thereof and blood lines via a blood compartment thereof, thetreatment fluid inlet pump actuator and treatment fluid outlet pumpactuator controlling a net transport of fluid between the non-blood andblood compartments during a treatment mode of a controller. Thetreatment fluid lines are selectively connectable by the controller toform a closed loop between an accumulator of the fluid circuit throughthe non-blood compartment. The treatment fluid lines are selectivelyconnectable, by the controller, between a treatment fluid source andsink and the non-blood compartment to form a circuit that bypasses theaccumulator of the fluid circuit. The treatment fluid inlet pumpactuator and treatment fluid outlet pump actuator are controlled by thecontroller, at a first time during a synchronization mode, to pump fluidthrough the closed loop and to detect a net transfer of fluid throughthe treatment device and responsively thereto, the controller storingdata indicative of the net transfer. The controller calculates a flowregulation parameter from the data. The treatment fluid inlet pumpactuator and treatment fluid outlet pump actuator are controlled by thecontroller responsively to the flow regulation parameter, at a secondtime during a treatment mode, to pump fluid from the source, through thenon-blood compartment, to the sink to perform a treatment. In additionalembodiments thereof, the twentieth embodiments include ones in which theaccumulator is a priming fluid bag connected to the treatment fluidlines.

In additional embodiments thereof, the twentieth embodiments includeones in which the net transfer of fluid through the treatment device isdetected by detecting a change in a weight or volume of the accumulator.In additional embodiments thereof, the twentieth embodiments includeones in which the sink is a collection container or a drain. Inadditional embodiments thereof, the twentieth embodiments include onesin which the body fluid is blood. In additional embodiments thereof, thetwentieth embodiments include ones in which the treatment fluid isdialysate and the treatment device is a dialyzer.

According to twenty-first embodiments, the disclosed subject matterincludes a method for controlling flow in a fluid circuit. The methodincludes providing a blood treatment system has a blood treatment devicewith a membrane that separates blood and non-blood compartments of theblood treatment device. The method includes pumping a blood-normal fluidthrough the non-blood compartment to prime it and pumping a primingfluid through the blood compartment. The method further includes pumpingblood through the blood compartment while halting a flow of blood-normalfluid and simultaneously sampling signals from pressure sensorsindicating a difference between the pressure of the non-bloodcompartment and the blood compartment. The method further includes usinga controller, storing pressure difference data responsive to thesampling and regulates a net transfer of fluid across the membraneduring a treatment cycle responsively to the pressure difference data.

In additional embodiments thereof, the twenty-first embodiments includeones in which the regulates includes controlling speeds of treatmentfluid pumps that pump fluid into and out of the blood treatment device.In additional embodiments thereof, the twenty-first embodiments includeones in which the regulating includes controlling speeds of treatmentfluid pumps that pump fluid into and out of the blood treatment device,the blood treatment device includes a dialyzer.

In additional embodiments thereof, the twenty-first embodiments includeones in which the regulating a net transfer of fluid across the membraneduring a treatment cycle includes repeating the pumping blood throughthe blood compartment while halting a flow of blood-normal fluidmultiple times during a treatment and detecting therefrom a change inthe pressure difference data between successive ones of the multipletimes. In additional embodiments thereof, the twenty-first embodimentsinclude ones in which the regulating a net transfer of fluid across themembrane during a treatment cycle further includes, between the multipletimes, reducing or halting the net transfer of fluid across the membraneand determining a treatment time or an ultrafiltration rate responsivelyto the pressure difference data between successive ones of the multipletimes, whereby a fluid rebound caused by fluid shifting in a patient tothe patient's blood compartment is indicated by the change in pressuredifference data between the successive ones is used to control the rateand/or extent of fluid withdrawal from a patient.

According to twenty-second embodiments, the disclosed subject matterincludes a system for controlling flow in a fluid circuit. A bloodtreatment machine is connected to a fluid circuit with a blood treatmentdevice with a membrane that separates blood and non-blood compartmentsof the blood treatment device. The blood treatment machine has aprogrammable controller connected to control a treatment fluid inflowpump, a treatment fluid outflow pump, a blood pump, and to receivepressure signals from one or more pressure sensors indicating thedifference between the pressures of the blood and non-bloodcompartments. An inflow pump is connected to a source of blood-normalfluid, the controller are programmed to control the inflow and outflowtreatment fluid pumps to pump fluid through the non-blood compartment toprime it during a non-treatment operating mode. A blood pump isconnected to the blood compartment, the controller are programmed topump a priming fluid through the blood compartment during thenon-treatment operating mode. The controller is programmed to pump bloodthrough the blood compartment while halting the inflow and outflowtreatment fluid pumps and simultaneously sample signals from the one ormore pressure sensors. The controller stores pressure difference dataresponsive to the sampling and controlling the inflow and outflowtreatment fluid pumps responsively to the pressure difference data toregulate a net transfer of fluid across the membrane during a treatmentcycle. In additional embodiments thereof, the twenty-second embodimentsinclude ones in which the blood treatment device includes a dialyzer. Inadditional embodiments thereof, the twenty-second embodiments includeones in which the controller regulates a net transfer of fluid acrossthe membrane during a treatment cycle by repeating the pumping bloodthrough the blood compartment while halting a flow of blood-normal fluidmultiple times during a treatment and detecting therefrom a change inthe pressure difference data between successive ones of the multipletimes. In additional embodiments thereof, the twenty-second embodimentsinclude ones in which the controller regulates a net transfer of fluidacross the membrane during a treatment cycle by repeating the pumpingblood through the blood compartment while halting a flow of blood-normalfluid multiple times during a treatment and detecting therefrom a changein the pressure difference data between successive ones of the multipletimes and, between the multiple times, reducing or halting the nettransfer of fluid across the membrane and determining a treatment timeor an ultrafiltration rate responsively to the pressure difference databetween successive ones of the multiple times, whereby a fluid reboundcaused by fluid shifting in a patient to the patient's blood compartmentis indicated by the change in pressure difference data between thesuccessive ones is used to control the rate and/or extent of fluidwithdrawal from a patient.

According to twenty-third embodiments, the disclosed subject matterincludes a method for controlling flow in a fluid circuit. The methodincludes using a controller of a treatment machine that controls flow offluids and blood in a fluid circuit, measuring oncotic pressure of bloodduring a treatment by halting a flow of a blood-normal treatment fluidin a blood treatment device separating flowing blood from the treatmentfluid while measuring a pressure difference between the treatment fluidand blood compartments of the blood treatment device. The methodincludes repeating the measuring multiple times during a treatment toobtain multiple oncotic pressure samples. The method includes comparinga trend in the oncotic pressure samples to a predefined trend anddetermining a treatment parameter therefrom. In additional embodimentsthereof, the twenty-third embodiments include ones in which thetreatment parameter includes a further duration of an on-goingtreatment. In additional embodiments thereof, the twenty-thirdembodiments include ones in which the treatment parameter includes anultrafiltration rate during an on-going treatment.

In additional embodiments thereof, the twenty-third embodiments includeones in which the controller reduces or increases a rate ofultrafiltration of the blood treatment device responsively to the trend.

According to twenty-fourth embodiments, the disclosed subject matterincludes a system for controlling flow in a fluid circuit. A bloodtreatment machine has a controller that controls flow of fluids andblood in a fluid circuit, the controller are programmed to selectivelyplace the fluid circuit in a condition for measuring oncotic pressure ofblood during a treatment by halting a flow of a blood-normal treatmentfluid in a blood treatment device separating flowing blood from thetreatment fluid while measuring a pressure difference between thetreatment fluid and blood compartments of the blood treatment device.The controller repeats the measuring multiple times during a treatmentto obtain multiple oncotic pressure samples. The controller compares atrend in the oncotic pressure samples to a predefined trend anddetermining a treatment parameter of a treatment delivered by the bloodtreatment machine responsively to the trend or a value of the oncoticpressure.

In additional embodiments thereof, the twenty-fourth embodiments includeones in which the treatment parameter includes a further duration of anon-going treatment. In additional embodiments thereof, the twenty-fourthembodiments include ones in which the treatment parameter includes anultrafiltration rate during an on-going treatment.

In additional embodiments thereof, the twenty-fourth embodiments includeones in which the controller reduces or increases a rate ofultrafiltration of the blood treatment device responsively to the trend.

According to twenty-fifth embodiments, the disclosed subject matterincludes method for controlling flow in a fluid circuit. The methodincludes providing a blood treatment system has a blood treatment devicewith a membrane that separates blood and non-blood compartments of theblood treatment device. The method includes pumping a blood-normal fluidthrough the non-blood compartment to prime it. The method includespumping a priming fluid through the blood compartment. The methodincludes pumping blood through the blood compartment while halting aflow of blood-normal fluid and simultaneously sampling signals frompressure sensors indicating a difference between the pressure of thenon-blood compartment and the blood compartment. The method includesusing a controller, storing property pressure difference data responsiveto the sampling and controlling the inflow and outflow treatment fluidpumps responsively to the pressure difference data to calculate a statusof a treatment, a blood property, or a fluid level of a patient aretreated and outputting data responsive to the status, property, or levelincludes one or more of: an amount of fluid to be removed from ortransferred to or from the patient or an estimated remaining time oftreatment.

In additional embodiments thereof, the twenty-fifth embodiments includeones in which the controller outputs the responsive data on a display orstores it in a treatment log.

According to twenty-sixth embodiments, the disclosed subject matterincludes a system for controlling flow in a fluid circuit. A bloodtreatment machine is connected to a fluid circuit with a blood treatmentdevice with a membrane that separates blood and non-blood compartmentsof the blood treatment device. The blood treatment machine has aprogrammable controller connected to control a treatment fluid inflowpump, a treatment fluid outflow pump, a blood pump, and to receivepressure signals from one or more pressure sensors indicating thedifference between the pressures of the blood and non-bloodcompartments. An inflow pump is connected to a source of blood-normalfluid, the controller are programmed to control the inflow and outflowtreatment fluid pumps to pump fluid through the non-blood compartment toprime it during a non-treatment operating mode. A blood pump isconnected to the blood compartment, the controller are programmed topump a priming fluid through the blood compartment during thenon-treatment operating mode. The controller is programmed to pump bloodthrough the blood compartment while halting the inflow and outflowtreatment fluid pumps and simultaneously sampling signals from the oneor more pressure sensors. The controller stores property pressuredifference data responsive to the sampling and controlling the inflowand outflow treatment fluid pumps responsively to the pressuredifference data to calculate a status of a treatment, a blood property,or a fluid level of a patient are treated and outputting data responsiveto the status, property, or level includes one or more of: an amount offluid to be removed from or transferred to the from the patient, anestimated remaining time of treatment, a plasma protein concentration,or a hematocrit of the patient.

In additional embodiments thereof, the twenty-sixth embodiments includeones in which the controller outputs the responsive data on a display orstores it in a treatment log.

According to twenty-seventh embodiments, the disclosed subject matterincludes a method for controlling flow in a fluid circuit. The methodincludes providing a treatment machine with a controller, pumps, and atleast one pressure sensor, the pumps are engaged with inflow and outflowlines to regulate flow therethrough responsively to the controller. Themethod includes connecting the inflow and outflow fluid lines to flowfluid to and from a patient, respectively, or to flow fluid to and froma treatment device connected to a patient, respectively. The methodincludes, at treatment times, using the controller, regulating a nettransport of fluid to the patient or the treatment device by controllingthe relative flow rates in the inflow and outflow lines. The methodincludes, at at least one synchronization time, using the controller,temporarily establishing a direct connection between the inflow andoutflow lines, bypassing the patient or the treatment device connectedto a patient and simultaneously using a predefined pressure sensor,detecting a difference between the flow rates in the inflow and outflowlines. The method includes, using the detected pressure in the detectingto regulate the net transport at one or more of the treatment times. Themethod includes, at a configuration time, after connecting the inflowand outflow lines, using the controller, detecting if there is aconnection error using the pressure sensor and outputting a signalindicating a result of the detecting on a user interface.

According to further embodiments, the disclosed subject matter includesa system for controlling flow in a fluid circuit. A treatment machinehas a programmable controller, pumps, and at least one pressure sensor,the pumps are engaged with inflow and outflow lines to regulate flowtherethrough responsively to the controller. The inflow and outflowfluid lines are connectable to a patient access or a blood treatmentdevice and arranged to flow fluid to and from a patient, respectively,or to flow fluid to and from the treatment device connected to apatient, respectively. The controller is programmed to, at treatmenttimes, regulate a net transport of fluid to the patient or the treatmentdevice by controlling the relative flow rates in the inflow and outflowlines. The controller is programmed to, at at least one synchronizationtime, temporarily establish a direct connection between the inflow andoutflow lines such that the patient or the treatment device connected toa patient is bypassed. At the at least at synchronization time, thecontroller samples and storing pressure signals from a predefinedpressure sensor to detect a difference between the flow rates in theinflow and outflow lines and calculate a flow control parameter from thestored samples. The controller thereafter uses the flow controlparameter to regulate the net transport at one or more of the treatmenttimes. The controller is further programmed to receive a set-up signalindicating that the patient access or the treatment device has beenconnected to the inflow and outflow lines and in response thereto,detect whether there is a connection error using the predefined pressuresensor and to output a signal responsive to the detection.

According to further embodiments, the disclosed subject matter includesa method for controlling flow in a fluid circuit. The method includesusing a controller, regulates the flow of fluid across a blood treatmentdevice membrane contacting a blood flow path responsively to a pressuresignal indicating pressure in the blood treatment device. The regulatingincludes controlling speeds of inflow and outflow pumps, the inflow pumppumping treatment fluid into the blood treatment device and the outflowpump pumping treatment fluid out of the blood treatment deviceresponsively to a target pressure on a blood and/or treatment fluid sideof the membrane. The method includes using the controller, at asynchronization time prior to the regulates, obtaining and storing thetarget pressure in a data store of the controller. The target pressureare calculated from a detected pressure on the blood and/or treatmentfluid side of the membrane at a time when the inflow and outflow pumpsare halted. The controller, at the synchronization time, halts theinflow and outflow pumps.

According to further embodiments, the disclosed subject matter includesa system for controlling flow in a fluid circuit. A treatment machinehas a fluid circuit engaged with first, second, and third pumpingactuators. The treatment machine has a controller connected to controlthe first, second, and third pumping actuators to perform a therapeutictreatment by regulates the flow fluid in the fluid circuit. The fluidcircuit has a treatment device that interconnects first fluid lines viaa first compartment thereof and second fluid lines via a secondcompartment thereof, the first and second pumping actuators controllinga net transport of fluid between the first and second compartmentsduring a treatment mode, the pressure sensor indicating a pressure ofthe first and/or second compartment. The first and second pumpingactuators are controlled by the controller, at a first time during asynchronization mode, to block flow in the first fluid lines whilepumping fluid through the second compartment at a predefined flow rateand to simultaneously store pressure data responsive to a pressuresignal from the pressure sensor. The first and second pumping actuatorsare controlled by the controller, at a second time during a treatmentmode to pump fluid through the second compartment at the predefined flowrate while simultaneously controlling flow in the first fluid linesresponsively to the pressure data.

According to further embodiments, the disclosed subject matter includesa method for controlling flow in a fluid circuit. The method applies toa hemofiltration machine with a controller that controls a netultrafiltration by independently regulates the speed of a waste pumpthat draws fluid from a hemofilter and the speed of a replacement fluidpump that pumps replacement fluid into a patient blood line, using thecontroller to control the pumps to implement synchronization andtreatment modes. According to the method, in a synchronization mode, thecontroller detecting a target pressure at an inlet of the waste pumpwhile flowing blood through the hemofilter and while blocking flowthrough the replacement fluid and waste pumps. Subsequently, in thesynchronization mode, the controller connects the replacement fluid pumpand the waste pump directly in series and, while flowing replacementfluid between them and controlling the waste pump speed to establish apredetermined hemofiltration rate, controlling the replacement fluidpump speed to determine a synchronized replacement fluid pump speed thatmaintains the waste pump inlet pressure at the target pressure.Subsequently, in a treatment mode, the controller connects thereplacement fluid pump to pump replacement fluid into a blood circuit atthe synchronized replacement pump speed.

According to further embodiments, the disclosed subject matter includesa system for controlling flow in a fluid circuit. A hemofiltrationmachine with fluid circuit has blood and non-blood portions, acontroller that controls waste and treatment fluid pumps connected to ahemofilter, a pressure sensor at an inlet of the waste pump, and flowcontrollers permitting selective interconnection of the blood andnon-blood portions. The waste pump draws fluid from a hemofilter and thereplacement fluid pump pumping replacement fluid into the blood portion.The controller controls a net ultrafiltration, during a treatment mode,by independently regulates the speeds of the waste and replacement fluidpumps. The controller is programmed to establish a synchronization modein which the controller detects a target pressure from the pressuresensor while flowing blood through the hemofilter and while halting flowthrough the replacement fluid and waste pumps. Subsequently, in thesynchronization mode, the controller connects the replacement fluid pumpand the waste pump directly in series through the non-blood portion,flowing replacement fluid between the pumps and controlling the wastepump speed establish a predetermined hemofiltration rate, controllingthe replacement fluid pump speed to determine a synchronized replacementpump speed that maintains the waste pump inlet pressure at the targetpressure. Subsequently, in the treatment mode, the controller connectsthe replacement fluid pump to pump replacement fluid into the bloodportion at the synchronized replacement pump speed.

According to twenty-eighth embodiments, the disclosed subject matterincludes a method for controlling flow in a fluid circuit. The methodapplies to a hemodiafiltration machine with a controller that controls anet ultrafiltration by independently regulates the speed of a waste pumpthat draws fluid from a hemodiafilter, the speed of a dialysate pumpthat pumps dialysate into the hemodiafilter, and the speed of areplacement fluid pump that pumps replacement fluid into a patient bloodline, using the controller to control the pumps to implement first andsecond synchronization and treatment modes. In the first synchronizationmode, the controller detects a first target pressure at an inlet of thewaste pump and a second target pressure equal to the average of pressureat the outlet of the dialysate pump and the pressure at the inlet of thewaste pump both while flowing blood through the hemodiafilter and whileblocking flow through the replacement fluid and waste pumps.Subsequently, in the first synchronization mode, the controller pumpsdialysate through the hemodiafilter using the dialysate and waste pumpsand controlling the waste pump speed to establish a predetermineddialysate flow rate, controlling the dialysate pump speed to determine asynchronized dialysate pump speed that maintains the average of theoutlet of the dialysate pump and the pressure at the inlet of the wastepump at the second target pressure. Subsequently, in the secondsynchronization mode, the controller connects the replacement fluid pumpand the waste pump directly in series and, while flowing replacementfluid between them and controlling the waste pump speed establish apredetermined hemofiltration rate, controlling the replacement fluidpump speed to determine a synchronized replacement fluid pump speed thatmaintains the waste pump inlet pressure at the first target pressure.Subsequently, in a treatment mode, the controller connects thereplacement fluid pump to pump replacement fluid into the blood portionat the synchronized replacement fluid pump speed, connect the dialysatepump to pump dialysate into the hemodiafilter at the synchronizeddialysate pump speed, and to connect the waste pump to draw waste fluidfrom the hemodiafilter at a rate responsive to the predetermineddialysate flow rate and the predetermined hemofiltration rate.

In additional embodiments thereof, the twenty-eighth embodiments includeones in which in the treatment mode, the waste pump is controlled todraw waste fluid from the hemodiafilter at a rate equal to the sum ofthe predetermined dialysate flow rate and the predeterminedhemofiltration rate.

According to twenty-ninth embodiments, the disclosed subject matterincludes a system for controlling flow in a fluid circuit. Ahemofiltration machine has fluid circuit has blood and non-bloodportions, a controller waste, dialysate, and treatment fluid pumpsconnected to a hemodiafilter, a pressure sensor at an inlet of the wastepump, and flow controllers permitting selective interconnection of theblood and non-blood portions. The controller controls a netultrafiltration, during a treatment mode, by independently regulates thespeed of the waste pump that draws fluid from a hemodiafilter, the speedof a replacement fluid pump that pumps replacement fluid into the bloodportion, and the speed of the dialysate pump that pumps dialysate intothe hemodiafilter. The controller controls the pumps to implement firstand second synchronization modes and a treatment mode. In the firstsynchronization mode, the controller detects a target pressure at aninlet of the waste pump while flowing blood through the hemodiafilterand while blocking flow through the replacement fluid and waste pumps.Subsequently, in the first synchronization mode, the controller pumpsdialysate through the hemodiafilter using the dialysate and waste pumpsand controlling the waste pump speed to establish a predetermineddialysate flow rate, controlling the dialysate pump speed to determine asynchronized dialysate pump speed that maintains the waste pump inletpressure at the target pressure. Subsequently, in the secondsynchronization mode, the controller connects the replacement fluid pumpand the waste pump directly in series and, while flowing replacementfluid between them and controlling the waste pump speed establish apredetermined hemofiltration rate, controlling the replacement fluidpump speed to determine a synchronized replacement fluid pump speed thatmaintains the waste pump inlet pressure at the target pressure.Subsequently, in a treatment mode, the controller connects thereplacement fluid pump to pump replacement fluid into the blood portionat the synchronized replacement fluid pump speed, connect the dialysatepump to pump dialysate into the hemodiafilter at the synchronizeddialysate pump speed, and to connect the waste pump to draw waste fluidfrom the hemodiafilter at a rate responsive to the predetermineddialysate flow rate and the predetermined hemofiltration rate. Inadditional embodiments thereof, the twenty-ninth embodiments includeones in which wherein, in the treatment mode, the waste pump iscontrolled to draw waste fluid from the hemodiafilter at a rate equal tothe sum of the predetermined dialysate flow rate and the predeterminedhemofiltration rate.

According to thirtieth embodiments, the disclosed subject matterincludes a method for controlling flow in a fluid circuit. The methodapplies to a treatment machine that controls the total volume of fluidflowing into or from a patient against the total volume of fluid drawnfrom the patient by regulates the relative speeds of peristaltic pumpsthat flow fluid in a fluid circuit connected to the patient. The methodincludes implementing a priming mode in which priming fluid is pumpedthrough the fluid circuit the priming mode includes pumping fluidthrough the fluid pumps for a break-in interval of at least five minutesbefore establishing a treatment mode in which the peristaltic pumps areused to control a net flow of fluid into or from the patient. Inadditional embodiments thereof, the thirtieth embodiments include onesin which the treatment machine is a hemodialysis machine and the pumpsregulate the flow of dialysate into and out of a dialyzer. In additionalembodiments thereof, the thirtieth embodiments include ones that furtherinclude, after the break-in interval, performing a flow calibrationprocedure in which the flow of one of the peristaltic pumps iscalibrated against a standard or another of the peristaltic pumps. Inadditional embodiments thereof, the thirtieth embodiments include onesin which the calibration procedure generates a control parameter that isused by the controller to regulate the peristaltic pumps during thetreatment mode.

It will be appreciated that the modules, controllers, processes,systems, and sections described above can be implemented in hardware,hardware programmed by software, software instruction stored on anon-transitory computer readable medium or a combination of the above.For example, a method for balancing fluid flow can be implemented, forexample, using a processor configured to execute a sequence ofprogrammed instructions stored on a non-transitory computer readablemedium. For example, the processor can include, but not be limited to, apersonal computer or workstation or other such computing system thatincludes a processor, microprocessor, microcontroller device, or iscomprised of control logic including integrated circuits such as, forexample, an Application Specific Integrated Circuit (ASIC). Theinstructions can be compiled from source code instructions provided inaccordance with a programming language such as Java, C++, C#.net or thelike. The instructions can also comprise code and data objects providedin accordance with, for example, the Visual Basic™ language, LabVIEW, oranother structured or object-oriented programming language. The sequenceof programmed instructions and data associated therewith can be storedin a non-transitory computer-readable medium such as a computer memoryor storage device which may be any suitable memory apparatus, such as,but not limited to read-only memory (ROM), programmable read-only memory(PROM), electrically erasable programmable read-only memory (EEPROM),random-access memory (RAM), flash memory, disk drive and the like.

Furthermore, the modules, processes, systems, and sections can beimplemented as a single processor or as a distributed processor.Further, it should be appreciated that the steps mentioned above may beperformed on a single or distributed processor (single and/ormulti-core). Also, the processes, modules, and sub-modules described inthe various figures of and for embodiments above may be distributedacross multiple computers or systems or may be co-located in a singleprocessor or system. Exemplary structural embodiment alternativessuitable for implementing the modules, sections, systems, means, orprocesses described herein are provided below.

The modules, processors or systems described above can be implemented asa programmed general purpose computer, an electronic device programmedwith microcode, a hard-wired analog logic circuit, software stored on acomputer-readable medium or signal, an optical computing device, anetworked system of electronic and/or optical devices, a special purposecomputing device, an integrated circuit device, a semiconductor chip,and a software module or object stored on a computer-readable medium orsignal, for example.

Embodiments of the method and system (or their sub-components ormodules), may be implemented on a general-purpose computer, aspecial-purpose computer, a programmed microprocessor or microcontrollerand peripheral integrated circuit element, an ASIC or other integratedcircuit, a digital signal processor, a hardwired electronic or logiccircuit such as a discrete element circuit, a programmed logic circuitsuch as a programmable logic device (PLD), programmable logic array(PLA), field-programmable gate array (FPGA), programmable array logic(PAL) device, or the like. In general, any process capable ofimplementing the functions or steps described herein can be used toimplement embodiments of the method, system, or a computer programproduct (software program stored on a non-transitory computer readablemedium).

Furthermore, embodiments of the disclosed method, system, and computerprogram product may be readily implemented, fully or partially, insoftware using, for example, object or object-oriented softwaredevelopment environments that provide portable source code that can beused on a variety of computer platforms. Alternatively, embodiments ofthe disclosed method, system, and computer program product can beimplemented partially or fully in hardware using, for example, standardlogic circuits or a very-large-scale integration (VLSI) design. Otherhardware or software can be used to implement embodiments depending onthe speed and/or efficiency requirements of the systems, the particularfunction, and/or particular software or hardware system, microprocessor,or microcomputer being utilized. Embodiments of the method, system, andcomputer program product can be implemented in hardware and/or softwareusing any known or later developed systems or structures, devices and/orsoftware by those of ordinary skill in the applicable art from thefunction description provided herein and with a general basic knowledgeof controllers and especially digital controllers and/or computerprogramming arts.

Moreover, embodiments of the disclosed method, system, and computerprogram product can be implemented in software executed on a programmedgeneral purpose computer, a special purpose computer, a microprocessor,or the like.

It is, thus, apparent that there is provided, in accordance with thepresent disclosure, flow balancing devices, methods and systems. Manyalternatives, modifications, and variations are enabled by the presentdisclosure. Features of the disclosed embodiments can be combined,rearranged, omitted, etc., within the scope of the invention to produceadditional embodiments. Furthermore, certain features may sometimes beused to advantage without a corresponding use of other features.Accordingly, Applicants intend to embrace all such alternatives,modifications, equivalents, and variations that are within the spiritand scope of the present invention.

The invention claimed is:
 1. A method for controlling fluid flow in afluid circuit, comprising: providing a blood treatment device having ablood compartment and a non-blood compartment separated from each otherby a membrane; connecting a first inflow line and a first outflow lineto one of the blood and the non-blood compartments of the bloodtreatment device; connecting a second inflow line and a second outflowline to the other of the blood and the non-blood compartments of theblood treatment device; using a controller, regulating a speed of afirst inflow pump fluidly connected to the first inflow line, toestablish a flow into said one of the blood and the non-bloodcompartments of the blood treatment device; using the controller,regulating a speed of a first outflow pump fluidly connected to thefirst outflow line to establish a flow out of said one of the blood andthe non-blood compartments of the blood treatment device; detecting apressure of at least one of the blood and the non-blood compartments,said pressure indicating a magnitude of a difference between rates ofthe flows into and out of said one of the blood and the non-bloodcompartments; during said detecting, blocking a flow of fluid throughthe second inflow and outflow lines such that the first inflow andoutflow lines and said one of the blood and the non-blood compartmentsof the blood treatment device constitute a fixed volume fluid channel;calculating a flow control parameter responsively to said pressure; andthereafter regulating a net transfer of fluid between the blood and thenon-blood compartments responsively to the control parameter.
 2. Themethod of claim 1, further comprising, during said detecting, flowingfluid through the second inflow and outflow lines.
 3. The method ofclaim 1, wherein the pressure indicates a magnitude of a transmembranetransport between the blood and the non-blood compartments.
 4. Themethod of claim 1, wherein the pressure indicates a magnitude of atransmembrane transport between the blood and the non-blood compartmentsand the calculating includes comparing the pressure to a predefinedthreshold pressure indicative of zero magnitude of the transmembranetransport between the blood and the non-blood compartments.
 5. Themethod of claim 1, wherein the pressure indicates a magnitude of atransmembrane transport between the blood and the non-bloodcompartments; the calculating includes comparing the pressure to apredefined threshold pressure indicative of zero magnitude of thetransmembrane transport between the blood and the non-bloodcompartments; and the method further includes determining the predefinedthreshold pressure by detecting a pressure of the at least one of theblood and the non-blood compartments while blocking transport betweenthe blood and the non-blood compartments.
 6. The method of claim 1,wherein the pressure indicates a magnitude of a transmembrane transportbetween the blood and the non-blood compartments; the calculatingincludes comparing the pressure to a predefined threshold pressureindicative of zero magnitude of the transmembrane transport between theblood and the non-blood compartments; and the method further includesdetermining the predefined threshold pressure by detecting a pressure ofthe at least one of the blood and the non-blood compartments whileblocking transport between the blood and the non-blood compartments andwhile establishing flow through the second inflow and outflow lines at apredefined flow rate.
 7. The method of claim 1, wherein the controllerincludes an embedded computer with a data store having instructionsreadable thereby to regulate, detect, and calculate and to store dataresponsive thereto.
 8. The method of claim 1, wherein the controlparameter includes a constant of proportionality that relates a commandspeed of a slave pump to a command speed of a master pump coincidingwith identical flow rates therethrough.
 9. The method of claim 1,wherein the controller adjusts the first outflow pump in response to apredefined ultrafiltration flow rate and said control parameter suchthat the first outflow pump generates a flow rate that is higher thanthat of the first inflow pump.
 10. The method of claim 1, wherein thecontroller continuously updates a speed of the first outflow pump inresponse to a signal from the detected pressure.
 11. The method of claim1, wherein the detected pressure of at least one of the blood and thenon-blood compartments is indicated by at least one of a pressure in thefirst inflow line and a pressure in the first outflow line.
 12. Themethod of claim 11, wherein the pressure of at least one of the bloodand the non-blood compartments is an average of the pressure in thefirst inflow line and the pressure in the first outflow line.
 13. Themethod according to claim 1, wherein the detecting the pressure of atleast one of the blood and the non-blood compartments is detecting thepressure of the blood compartment.
 14. A method for controlling flow ina blood treatment fluid circuit, the method comprising: pumping fluidserially through first fluid lines connected to second fluid linesthrough a blood treatment device while blocking flow through the secondfluid lines; the pumping including, using a controller to control speedsof pumping actuators, each of the pumping actuators determining a flowrate through a respective one of the first fluid lines; the first fluidlines being one of blood lines and treatment fluid lines and the secondlines being the other of blood lines and treatment fluid lines; usingthe controller, detecting sensor data indicating a difference betweensaid flow rates in the first fluid lines as well as speed dataindicating a speed of at least one of the pumping actuators; using thecontroller, calculating one or more control parameters from said speedand sensor data, the one or more control parameters indicating saidspeed of said at least one of the pumping actuators for which saiddifference is below a predefined threshold; and using the controller,regulating a net transfer of fluid through a pair of the first fluidlines to, or from, the blood treatment device by regulating the speedsof said at least one of the pumping actuators responsively to said oneor more control parameters.
 15. The method of claim 14, wherein thedetecting and calculating are performed during a synchronization modeand said regulating is performed during a treatment mode.
 16. The methodof claim 14, wherein the calculating includes feedback controlling theat least one of the pumping actuators responsively to the sensor data toachieve a target magnitude indicated by said sensor data.
 17. The methodof claim 14, wherein said sensor data is from a digitized pressuresensor signal, the pressure sensor indicating the pressure inside theblood treatment device.
 18. The method of claim 14, wherein said secondfluid lines are blood lines of a hemodialysis fluid circuit.
 19. Themethod of claim 18, wherein the blood treatment device is a dialyzer.20. The method of claim 14, wherein the regulating includes a nettransfer of fluid responsively to both the one or more controlparameters and a predefined ultrafiltration rate, such that a net flowfrom said blood treatment device through said first fluid lines, equalto said predefined ultrafiltration rate, is established.